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Purpose: To investigate whether genetic variations in cytokine genes involved in the pathogenesis of peri-implantitis are associated with the occurrence of peri-implantitis, an issue that remains controversial and may vary according to the population evaluated. Materials and Methods: A cross-sectional analytical study was carried out on 102 Caucasian Portuguese individuals who were divided into two groups: (1) 43 individuals with peri-implantitis and (2) 59 individuals with good peri-implant health. Samples from the buccal mucosa were obtained, and genetic analysis was performed using the real-time polymerase chain reaction (PCR) technique for IL-1A and IL-1B and PCR for IL-1RN. Results: The IL-1A-889 C/T polymorphism presented with a higher prevalence of the less common allele (T allele) in patients with peri-implantitis (27.9%) than in healthy patients (16.9%), but without statistical significance (P = .060). For the IL-1B+3954 C/T and IL-1RN (variable number of tandem repeats [VNTR]) polymorphisms, analysis revealed that the allele and genotype frequencies did not differ significantly between groups. There was a significant association between a history of periodontitis and peri-implantitis (P = .020). Conclusions: The evaluated genetic polymorphisms had no influence on the occurrence of peri-implantitis in the study population. Further research into genetic variations in different populations is needed to elucidate the role of genetic factors in the onset and progression of peri-implant disease. [ABSTRACT FROM AUTHOR]

Purpose: Injury prevention is a crucial aspect of sports, particularly in high-performance settings such as elite female football. This study aimed to develop an injury prediction model that incorporates clinical, Global-Positioning-System (GPS), and multiomics (genomics and metabolomics) data to better understand the factors associated with injury in elite female football players. Methods: We designed a prospective cohort study over 2 seasons (2019–20 and 2021–22) of noncontact injuries in 24 elite female players in the Spanish Premiership competition. We used GPS data to determine external workload, genomic data to capture genetic susceptibility, and metabolomic data to measure internal workload. Results: Forty noncontact injuries were recorded, the most frequent of which were muscle (63%) and ligament (20%) injuries. The baseline risk model included fat mass and the random effect of the player. Six genetic polymorphisms located at the DCN, ADAMTS5, ESRRB, VEGFA, and MMP1 genes were associated with injuries after adjusting for player load (P <.05). The genetic score created with these 6 variants determined groups of players with different profile risks (P = 3.1 × 10−4). Three metabolites (alanine, serotonin, and 5-hydroxy-tryptophan) correlated with injuries. The model comprising baseline variables, genetic score, and player load showed the best prediction capacity (C-index:.74). Conclusions: Our model could allow efficient, personalized interventions based on an athlete's vulnerability. However, we emphasize the necessity for further research in female athletes with an emphasis on validation studies involving other teams and individuals. By expanding the scope of our research and incorporating diverse populations, we can bolster the generalizability and robustness of our proposed model. [ABSTRACT FROM AUTHOR]

Flavonoids exert vasculoprotective effects in humans, but interindividual variability in their action has also been reported. This study aims to identify genes that are associated with vascular health effects of flavonoids and whose polymorphisms could explain interindividual variability in response to their intake. Applying the predetermined literature search criteria, we identified five human intervention studies reporting positive effects of flavonoids on vascular function together with global genomic changes analyzed using microarray methods. Genes involved in vascular dysfunction were identified from genome-wide association studies (GWAS). By extracting data from the eligible human intervention studies, we obtained 5807 differentially expressed genes (DEGs). The number of identified upstream regulators (URs) varied across the studies, from 227 to 1407. The search of the GWAS Catalog revealed 493 genes associated with vascular dysfunction. An integrative analysis of transcriptomic data with GWAS genes identified 106 candidate DEGs and 42 candidate URs, while subsequent functional analyses and a search of the literature identified 20 top priority candidate genes: ALDH2, APOE, CAPZA1, CYP11B2, GNA13, IL6, IRF5, LDLR, LPL, LSP1, MKNK1, MMP3, MTHFR, MYO6, NCR3, PPARG, SARM1, TCF20, TCF7L2, and TNF. In conclusion, this integrated analysis identifies important genes to design future nutrigenetic studies for development of precision nutrition for polyphenols.

Objective: The pathogenesis of antituberculosis drug-induced liver injury (AT-DILI) remains largely unknown. The current investigation aimed to determine the genetic contribution of the nuclear receptor subfamily 1 Group I member 3 (NR1I3) and nuclear receptor subfamily 1 Group H member 4 (NR1H4) genes to the risk of AT-DILI in the Chinese population. Methods: A 1:4 matched case‒control study was conducted, and five single nucleotide polymorphisms (SNPs) in the NR1I3 and NR1H4 genes were detected and assessed. Utilizing a multivariate conditional logistic regression model, the effects of haplotype and genotype on the risk of AT-DILI were examined. Extended subgroup analysis was carried out based on sex. The distribution of the peak value of serum liver enzymes also compared among different genotypes. Results: 224 AT-DILI cases and 896 controls were included in this study. No significant difference was observed in genotypes or haplotypes frequencies between AT-DILI cases and controls. However, comparisons of liver function indicators revealed significant differences in the peak values of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) among patients with different genotypes of NR1H4 rs56163822 (GG vs. GT vs. TT, 27.1 U/L vs. 26.0 U/L vs. 23.0 U/L, p = 0.020; 34.0 U/L vs. 31.0 U/L vs. 30.6 U/L, p = 0.008; 15.5 μmol/L vs. 15.0 μmol/L vs. 13.7 μmol/L, p = 0.029, respectively), as well as in the peak values of ALT and AST among male patients with different genotypes of NR1H4 rs56163822 (29.0 U/L vs. 26.9 U/L vs. 22.6 U/L, p = 0.002; 34.0 U/L vs. 32.0 U/L vs. 30.5 U/L, p = 0.019, respectively). Conclusion: Based on this 1:4 individual-matched case‒control study, the SNP rs56163822 in the NR1H4 gene may be linked to the susceptibility to AT-DILI in Chinese patients receiving anti-TB treatment. Further studies in larger varied populations are needed to validate our findings. [ABSTRACT FROM AUTHOR]

Context.--High-grade transformation, previously known as dedifferentiation, in salivary gland carcinoma and carcinosarcoma ex pleomorphic adenoma is a rare phenomenon. It is, however, clinically relevant and affects treatment and prognosis. Objective.--To review the existing literature, describe the histologic and immunophenotypic features, and highlight the diagnostic criteria of high-grade transformation in various salivary gland carcinomas and carcinosarcomas; to review its effect on clinical presentation and prognosis; and to review relevant molecular characteristics and recent concepts and advances. Data Sources.--Literature search in PubMed using key words such as "high-grade transformation," "dedifferentiation," and "carcinosarcoma" in salivary gland. Relevant articles were reviewed, and additional articles were curated from the references of these articles. Conclusions.--High-grade transformation occurs rarely but has a significant impact on prognosis and management. By microscopy, the high-grade area is usually a distinct nodule and shows solid and nested architecture, cellular atypia, high mitotic count, and necrosis. The molecular features are not well established. Carcinosarcoma almost always arises in a pleomorphic adenoma and likely follows an adenoma-carcinoma-sarcoma pathway. [ABSTRACT FROM AUTHOR]

ABSTRACT Previous observational studies focused on the association of tea intake and allergic diseases. However, it is not known whether these associations are causal. We used a bidirectional Mendelian randomization (MR) study to assess the causal relationship of tea intake with the risk of allergic diseases, such as atopic dermatitis (AD), allergic rhinitis (AR), and allergic asthma (AA). Single‐nucleotide polymorphisms (SNPs) which had genetic statistical significance with tea intake were used as instrumental variables (IVs). We employed heritable IVs of tea intake from the UK Biobank, which included 447,485 samples. Sensitivity analyses were further performed using MR Egger and MR‐PRESSO. Inverse variance weighted (IVW) method was used as the main approach. In this MR study, 40 independent SNPs were selected for tea intake. The MR analysis revealed that an increase in genetically predicted tea intake was associated with a lower risk of AD (OR = 0.709, 95% CI = 0.546–0.919, p = 0.009). Furthermore, we observed a causal effect of genetically predicted tea intake on the risk of AA (OR = 0.498, 95% CI = 0.320–0.776, p = 0.002). However, no significant causal relationship was found between genetically predicted tea intake and AR (OR = 1.008, 95% CI = 0.998–1.017, p = 0.115). Our MR analysis suggested that increased tea intake may reduce the risk of AD and AA in European population. This suggests that tea intake is likely a trigger or a prevention strategy for AD and AA. [ABSTRACT FROM AUTHOR]

As detailed information on the pharmacokinetics (PK) of labetalol in pregnant people are lacking, the aims of this study were: (1) to build a physiologically based PK (PBPK) model of labetalol in non‐pregnant individuals that incorporates different CYP2C19 genotypes (specifically, *1/*1, *1/*2 or *3, *2/*2, and *17/*17); (2) to translate this model to the second and third trimester of pregnancy; and (3) to combine the model with a previously published direct pharmacodynamic (PD) model to predict the blood pressure lowering effect of labetalol in the third trimester. Clinical data for model evaluation was obtained from the scientific literature. In non‐pregnant populations, the mean ratios of simulated versus observed peak concentration (Cmax), time to reach Cmax (Tmax), and exposure (area under the plasma concentration–time curve, AUC) were 0.94, 0.82, and 1.16, respectively. The pregnancy PBPK model captured the observed PK adequately, but clearance was slightly underestimated with mean ratios of simulated versus observed Cmax, Tmax, and AUC of 1.28, 1.30, and 1.39, respectively. The results suggested that pregnant people with CYP2C19 *2/*2 alleles have similar labetalol exposure and trough levels compared to non‐pregnant controls, whereas those with other alleles were found to have increased exposure and trough concentrations. Importantly, the pregnancy PBPK/PD model predicted that, despite increased exposure in some genotypes, the blood pressure lowering effect was broadly comparable across all genotypes. In view of the large inter‐individual variability and the potentially increasing blood pressure during pregnancy, patients may need to be closely monitored for achieving optimal therapeutic effects and avoiding adverse events. [ABSTRACT FROM AUTHOR]

Several investigations have been carried out to explore the genetic association of TLR4 codon variants, specifically Asp299Gly and Thr399Ile, and susceptibility to sepsis, but the results have been contradictory. The present study aimed to conduct a meta‐analysis to draw a definitive conclusion regarding the role of TLR4 genetic variants (Asp299Gly and Thr399Ile) in sepsis. A thorough literature search was conducted using the PubMed, Scopus, and Science Direct databases. The inclusion and exclusion criteria were established to ensure the accuracy of the data. The Comprehensive Meta‐Analysis Software v4 was utilized to perform the meta‐analysis and related analyses. A total of 13 studies were analyzed, including 2328 sepsis cases and 2495 healthy controls for the TLR4 Asp299Gly variant. Eight studies provided genotype data for the rs4986791 polymorphism. The Asp299Gly variant showed a marginal protective effect in the allele (p = 0.08, odds ratio = 0.71) and dominant (p = 0.09, odds ratio = 0.71) genetic models, although it was not statistically significant. The trial sequential analysis indicated that further case–control studies are necessary to draw definitive conclusions about the TLR4 polymorphisms in sepsis. The TLR4 Asp299Gly variant may have a protective effect against sepsis. However, additional research with larger sample sizes across diverse populations is required to validate this finding. [ABSTRACT FROM AUTHOR]

Background: Gouty arthritis is a metabolic disease characterized by the deposition of monosodium urate crystals in the joints, which triggers the release of interleukin-1β (IL-β) by activating the NLRP3 inflammasome. Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor involved in IL-β production and as a regulator of NLRP3. Objectives: The aims were to analyze the association of HIF1A rs11549465, rs11549467, and rs2057482 variants in patients with gouty arthritis, and to evaluate the correlation between urate and HIF-1α levels according to the associated genotypes. Methods: Cases and controls were genotyped using TaqMan probes, and urate and HIF-1α levels were quantified. Data were analyzed using SPSS v21 software and P-values < 0.05 were considered statistically significant. Results: Urate and HIF-1α levels were higher in patients than in controls (P < 0.05). Under the three inheritance models (codominant, dominant, and recessive), the AA genotype of the rs11549467 variant was associated with gout risk (OR = 5.74, P = 0.009, OR = 3.33, P = 0.024, and OR = 9.09, P = 0.003, respectively). There were significant differences in the distribution of serum levels of both HIF-1α (P < 0.0001) and urate (P = 0.016) according to the genotypes of the rs11549467 variant. Conclusion: These results suggest that the HIF1A rs11549467 variant may play a key role in the pathogenesis of gouty arthritis. Key Points • The pathogenesis of gouty arthritis involves the HIF1A gene. • In patients with gout, the AA genotype of the rs11549467 (HIF1A) variant is associated with increased serum levels of urate and HIF-1α. • HIF-1α is involved in the regulation of IL-1β and NLRP3. [ABSTRACT FROM AUTHOR]

Single nucleotide polymorphisms (SNPs) of the protein tyrosine phosphatase non-receptor type 2 (PTPN2) gene have been documented to be linked with several autoimmune disorders including Behçet's disease (BD). PTPN2 SNPs rs2542151 and rs7234029 have been assessed using real-time PCR in 96 BD patients and 50 controls matched by age and gender. Patients were categorized into groups according to the disease phenotypes and severity. A total of 94.8% of patients were males. The patients' mean age at onset was 26.1 ± 8 years. The median (IQR) disease duration was 8.5(4–13) years. No difference was observed between the patients and controls concerning the frequency of the two SNPs' different genotypes, models, and alleles. Moreover, neither disease phenotypes nor severity were associated with rs2542151 or rs7234029 SNPs. PTPN2 rs2542151 and rs7234029 SNPs do not seem to have associations with BD occurrence, phenotypes, or severity in the Egyptian patients. Key Points • PTPN2 rs2542151 and rs7234029 SNPs do not seem to have associations with BD occurrence, phenotypes, or severity in the Egyptian patients. • Further studies involving a larger sample size with variable clinical diversity are recommended to verify the results. [ABSTRACT FROM AUTHOR]

Genetic polymorphisms in the sodium taurocholate cotransporting peptide (NTCP encoded by SLC10A1) have been described, but their role in untreated and treated patients with chronic hepatitis delta (CHD) remains unknown. Virological response (VR) to the NTCP inhibitor bulevirtide (BLV) was achieved at week 48 by >70% of patients with CHD, but nearly 15% experienced virological non-response (VNR) or partial response (PR). This study aimed to evaluate whether NTCP genetic polymorphisms affect baseline HDV RNA load and response to BLV in patients with CHD. BLV-untreated and -treated patients were enrolled in a retrospective cross-sectional and longitudinal study. Clinical and virological characteristics were collected at baseline and up to 96 weeks in the BLV-treated patients. NTCP genetic polymorphisms were identified by Sanger sequencing. Of the six NTCP polymorphisms studied in 209 untreated patients with CHD, carriers of the rs17556915 TT/CC (n = 142) compared to CT (n = 67) genotype presented with higher median HDV RNA levels (5.39 vs. 4.75 log 10 IU/ml, p = 0.004). Of 209 patients receiving BLV monotherapy at 2 mg/day, 76 were evaluated at week 24 and 40 up to week 96. Higher mean baseline HDV RNA levels were confirmed in TT/CC (n = 43) compared to CT (n = 33) carriers (5.38 vs. 4.72 log 10 IU/ml, p = 0.010). Although 24-week VR was comparable between TT/CC and CT carriers (25/43 vs. 17/33, p = 0.565), the former group presented VNR more often than PR (9/11 vs. 9/23, p = 0.02) at week 24. 7/9 TT/CC genotype carriers remained VNR at week 48 of BLV treatment. The NTCP rs17556915 C>T genetic polymorphisms may influence baseline HDV RNA load both in BLV-untreated and -treated patients with CHD and may contribute to identifying patients with different early virological responses to BLV. Although several sodium taurocholate cotransporting polypeptide (NTCP) genetic polymorphisms have been described, no data are available on their potential role in modifying HDV RNA load or treatment response to bulevirtide (BLV) in patients with chronic hepatitis delta (CHD). In this study, we demonstrated that patients with CHD, either treated or untreated, carrying NTCP rs17556915 TT/CC, presented higher baseline HDV RNA levels compared to those with the CT genotype. Higher HDV RNA levels in TT/CC carriers compared to CT carriers were also confirmed in patients with CHD treated with BLV monotherapy up to 96 weeks. Furthermore, carriers of TT/CC, compared to CT genotype, more frequently showed viral non-response (VNR) than partial response (PR) at week 24 of BLV treatment, and 7/9 TT/CC genotype carriers remained VNR at week 48 of BLV treatment. This is the first study demonstrating a potential role of NTCP genetic polymorphisms in influencing HDV viral load and early virological response to BLV monotherapy. Since no direct HDV resistance to BLV has been described so far, if confirmed in larger studies, the genetic polymorphisms in NTCP may help identify patients with different patterns of early virological response to BLV. [Display omitted] • The impact of NTCP genetic variants on HDV RNA load and treatment response to BLV in CHD is unknown. • Patients with CHD carrying NTCP rs17556915 TT/CC compared to CT genotypes presented higher baseline HDV RNA load. • Carriers of TT/CC compared to CT were more likely to show a viral non-response than a partial response at week 24 of BLV treatment. • C>T genetic polymorphisms seem to affect baseline HDV RNA load and may help identify different patterns of early virological response to BLV. [ABSTRACT FROM AUTHOR]

This study aimed to identify the specific vaccine strain associated with herpes zoster (HZ) in children following a series of diagnosed cases and to explore whether differences in single nucleotide polymorphisms (SNPs) among various vaccine strains are linked to an increased incidence of herpes zoster after vaccination. From February 2021 to March 2024, children <12 years old suspected of vaccine-related varicella-like rash or HZ were included. Varicella zoster virus DNA isolated from the patients were sequenced to differentiate vaccine type versus wild-type. 3D protein structures of pORF62 were simulated using open reading frame 62 sequences extracted from whole genome sequencing of vOka, MAV/06, Oka/SK vaccines, and pOka reference. A total of 27 children with a median age of 2.1 (interquartile range, 1.5–3.4) years old presented with vaccine-related varicella-like rash (n = 4/27, 14.8%) or HZ (n = 23/27, 85.2%). One patient with varicella-like rash and 34.8% (n = 8/23) with HZ had disseminated skin involvement. All were immunized with the Oka/SK strain varicella vaccine. Genotyping showed 88.2% (n = 15/17) had SNPs specific to the Oka/SK strain, and two had SNPs considered pOka type contained within the Oka/SK vaccine. Despite accumulations of SNPs in ORF 62 of Oka/SK, the translated amino acid sequence and 3D protein structure were identical to wild-type pOka's pORF62. In vOKA and MAV/06, changes in amino acids occurred at two positions, S628G and R958G, within pORF62. The predicted 3D protein structure of vOka and MAV/06's pORF62 showed that the α helical structure within region I undergoes conformational change, potentially increasing difficulties in interactions with infection-related proteins and thereby decreasing virulence. pORF62 in pOka and Oka/SK exhibited more stable structure complex of the α helical structure. Lack of structural alternations in region I of pORF62 due to the absence of critical genetic polymorphisms in open reading frame 62 could be associated with the heightened incidence of adverse events. [ABSTRACT FROM AUTHOR]

Purpose: Therapeutic drug monitoring (TDM) of voriconazole (VCZ) should be mandatory for all pediatric patients with invasive fungal infections (IFIs). The narrow therapeutic index, inter-individual variability in VCZ pharmacokinetics, and genetic polymorphisms cause achieving therapeutic concentration during therapy to be challenging in this population. Methods: The study included 44 children suffering from IFIs treated with VCZ. Trough concentrations (Ctrough) of VCZ ware determined by the HPLC-FLD method. Identification of the CYP2C19*2 and CYP2C19*17 genetic polymorphisms was performed by PCR–RFLP. The correlation between polymorphisms and VCZ Ctrough was analyzed. Moreover, the effect of factors such as dose, age, sex, route of administration, and drug interactions was investigated. Results: VCZ was administered orally and intravenously at a median maintenance dosage of 14.7 mg/kg/day for a median of 10 days. The VCZ Ctrough was highly variable and ranged from 0.1 to 6.8 mg/L. Only 45% of children reached the therapeutic range. There was no significant association between Ctrough and dosage, age, sex, route of administration, and concomitant medications. The frequencies of variant phenotype normal (NM), intermediate (IM), rapid (RM) and ultrarapid metabolizers (UM) were 41%, 18%, 28%, and 13%, respectively. Ctrough of VCZ were significantly higher in NM and IM groups compared with RM, and UM groups. Conclusion: The Ctrough of VCZ is characterized by inter-individual variability and a low rate of patients reaching the therapeutic range. The significant association exists in children between VCZ Ctrough and CYPC19 phenotype. The combination of repeated TDM and genotyping is necessary to ensure effective treatment. [ABSTRACT FROM AUTHOR]

There is little and conflicting data on the role of the plasminogen activator inhibitor-1 (PAI-1, SERPINE1) 4G/5G polymorphism in familial Mediterranean fever (FMF). Therefore this study aimed at evaluating the impact of this polymorphism on the disease course in a cohort of 303 Armenian FMF patients. Genotyping for 12 Mediterranean fever (MEFV) gene mutations and the PAI-1 4G/5G (rs1799762) polymorphism were performed by PCR/reverse-hybridization (StripAssay) and real-time PCR, respectively. PAI-1 genotypes 4G/4G, 4G/5G, and 5G/5G could be identified in 4 (5.88%), 30 (18.63%) and 9 (12.16%) patients with erysipelas-like erythema (ELE), while this was the case for 64 (94.12%), 131 (81.37%), and 65 (87.84%) patients without ELE, respectively (P < 0.033). We have identified a significant relationship between the PAI-1 4G/5G genotype and the occurence of ELE in a relatively large cohort of Armenian FMF patients. Because of conflicting results concerning the impact of this polymorphism on the clinical course of FMF in different populations, further studies are desirable to substantiate the findings reported here. [ABSTRACT FROM AUTHOR]

Knee osteoarthritis (KOA) is an important cause of disability in the world and it denotes a public health defiance of the upcoming years. Aim To examine the connection between ADAMTS14 gene rs4747096 polymorphism and KOA and to assess risk factors associated with KOA. Methods A case control study was conducted on 158 patients with KOA and 120 controls with comparable age and sex randomly recruited from National Research Centre employees. All participants were subjected to full history taking, assessment of KOA severity using WOMAC scoring system, and thorough clinical examination. Blood sample was collected for detection of ADAMTS14/rs4747096 gene polymorphism. Results The frequency of ADAMTS14 gene rs4747096 genotypes among patients with KOA was 73.5% for AA, 25.7% for AG, and 0.7% for GG compared to controls 963%, 31.3%, and 5.6% respectively and the frequency of alleles among patients was 86.4% for A and 78.7% for G compared to controls (78.7% and 21.3% respectively, P < 0.05. The study found that the median levels of total WOMAC score and its domains were significantly higher among KOA patients than controls. The logistic regression analysis revealed that age ≥ 50 years, BMI ≥ 35, and long standing at work were predictive factors for KOA (P < 0.05). Regarding different genetic patterns, only the A recessive pattern of inheritance was found to be a predictive risk factor for KOA. Conclusion For ADAMTS14 rs4747096 genotype, the AA and AG genotypes significantly increased the risk of KOA. The recessive pattern of inheritance, older age, morbid obesity, and prolonged standing at work were the predictive risk factors for KOA. Further studies with larger sample size are encouraged to investigate the mechanism by which this genotype can affect the development of KOA. [ABSTRACT FROM AUTHOR]

Background: Epidemiological studies have reported that polymorphisms of folate-metabolizing genes have a significant impact on male infertility. However, the results of published studies have come to different conclusions. Objective: To determine an association between folate-metabolizing gene polymorphisms and the risk of male infertility. Methods: The meta-analysis was conducted according to the PRISMA 2020 statement. The protocol was registered with PROSPERO (CRD42023412251). Studies were searched from PubMed, Google Scholar, Embase, Scopus, and the Cochrane Library up to 24st October2023. Articles that satisfied the inclusion criteria were evaluated for their quality using the Newcastle–Ottawa Scale. Data were extracted from the eligible studies and were analyzed for pooled up odds ratio (OR) with 95% confidence interval (CI). Meta-analysis was conducted using STATA 12. Results: Forty-six case–control studies were included in the meta-analysis which comprised 20,639 participants. The pooled analysis revealed that the MTHFR C677T polymorphism was significantly associated with male infertility and abnormospermia.Three-fifths of the model showed there was a significant association between the MTR A2756G polymorphism and male infertility. Both MTHFR A1298C and MTRR A66G polymorphisms were not significantly associated with male fertility. Furthermore, subgroup analysis revealed a significant association between the MTHFR C677T polymorphism and male fertility in Asian countries. Conclusion: This meta-analysis suggests that the MTHFR C677T and MTR A2756G polymorphisms may be a potential risk factor for male infertility. [ABSTRACT FROM AUTHOR]

Background: Microvascular complications of diabetes including retinopathy, nephropathy, and neuropathy are those long-term complications that affect small blood vessels. Diabetic nephropathy (DN) is characterized by persistent microalbuminuria. A meta-analysis of case–control studies aims to examine the relationship between MnSOD (rs4880) and GPx1 (rs1050450) and the risk of DN. Methods: Various databases such as Web of Science, PubMed, Springer Link, Cochrane Library, Science Direct, Embase, and Google Scholar were utilized to extract relevant studies. The statistical software MedCalc version 22.009 was acquired to accomplish the meta-analysis of the included studies. Results: A significant association was found between two SNPs (rs4880 and rs1050450) and DN in the homozygous recessive model [95% confidence interval (CI) 0.97–2.41, odds ratio (OR) TT vs CC = 1.53, P = 0.06] and heterozygous model [95% CI 0.92–1.97, OR CT vs CC = 1.35, P = 0.12], while there was no association with the other genetic models. A significant association between rs4880 and DN was perceived in the Asian population [95% CI 1.24–2.03, OR = 1.6, P < 0.001], meanwhile the studies among Caucasian group showed insignificant association [95% CI 0.87–1.32, OR = 1.07, P = 0.5]. On the other hand, the association between rs1050450 and DN was significant [95% CI 3.80–13.01, OR = 7.04, P < 0.001] and insignificant [95% CI 0.96–2.28, OR = 1.48, P = 0.07] among Asian and Caucasian population, respectively. Conclusion: To date, this meta-analysis could be the first to contribute a panoramic exploration of the MnSOD and GPx1 polymorphic association with DN. The results of the study contemplate the data presently accessible from the literature and can be employed as an influential lead for future research. [ABSTRACT FROM AUTHOR]

Background: Plasmodium falciparum merozoite surface proteins 1 (PfMSP1) and 2 (PfMSP2) are potential candidates for malaria vaccine development. However, the genetic diversity of these genes in the global P. falciparum population presents a significant challenge in developing an effective vaccine. Hence, understanding the genetic diversity and evolutionary trends in the global P. falciparum population is crucial. Methods: This study analyzed the genetic variations and evolutionary changes of pfmsp1 and pfmsp2 in P. falciparum isolates from the Central Highland and South-Central regions of Vietnam. DNASTAR and MEGA7 programs were utilized for analyses. The polymorphic nature of global pfmsp1 and pfmsp2 was also investigated. Results: A total of 337 sequences of pfmsp1 and 289 sequences of pfmsp2 were obtained. The pfmsp1 and pfmsp2 from Vietnam revealed a higher degree of genetic homogeneity compared to those from other malaria-endemic countries. Remarkably, the allele diversity patterns of Vietnam pfmsp1 and pfmsp2 differed significantly from those of neighboring countries in the Greater Mekong Subregion. Declines in allele diversity and polymorphic patterns of Vietnam pfmsp1 and pfmsp2 were observed. Conclusions: The Vietnam P. falciparum population might be genetically isolated from the parasite populations in other neighboring GMS countries, likely due to geographical barriers and distinct evolutionary pressures. Furthermore, bottleneck effects or selective sweeps may have contributed to the genetic homogeneity of Vietnam pfmsp1 and pfmsp2. [ABSTRACT FROM AUTHOR]

All the factors potentially influencing tacrolimus dose requirement and combinations thereof have never been thoroughly investigated, precluding accurate prediction of tacrolimus starting dose. This prospective, non-interventional, multicenter study in de novo adult kidney transplant recipients over the first year after transplantation aimed to investigate the factors influencing tacrolimus dose-standardized trough blood concentration (C0/D) over the first week post-transplant (D4-D7, primary objective), D8-M3 and M3-M12 (secondary objectives). Statistical analysis employed mixed linear models with repeated measures. Eighteen sites enrolled 440 patients and followed them up for 9.5 ± 4.1 months. Age at baseline (p = 0.0144), end-stage renal disease (p = 0.0092), CYP3A phenotype (p < 0.0001), dyslipidemia at baseline (p = 0.0031), hematocrit (p = 0.0026), total bilirubin (p = 0.0261) and plasma creatinine (p = 0.0484) independently increased with log(C0/D) over D4-D7, explaining together 72.3% of the interindividual variability, and representing a robust model to estimate tacrolimus initial dose. Donor age and CYP3A phenotype were also influential over D8-M3 and M3-12, in addition to recipient age. Corticosteroids, diabetes at baseline, and ASAT yielded inconstant results between D8-M3 and M3-M12. We found no ethnicity effect when CYP3A phenotype was accounted for, and no food effect. Intra-individual variability over M3-M12 was moderate, and significantly lower in patients with chronic hepatic disorder (p = 0.0196) or cancer (p = 0.0132). [ABSTRACT FROM AUTHOR]

Objective To comprehensively evaluate the association between Thymic Stromal Lymphopoietin (TSLP) and atopic dermatitis (AD). Methods Six databases were searched for relevant studies. For studies on TSLP levels, the standardized mean difference (SMD) was used. For studies involving gene polymorphisms, evaluation was performed using odds ratios (ORs) and 95% confidence intervals (95% CIs). Based on the between-study heterogeneity, a fixed- or random-effects model was chosen. Analyses were performed using RevMan 5.3 software and R 4.3.0 software. Trial sequential analysis was conducted to evaluate whether the number of cases was sufficient. Results A significant relationship between TSLP rs1898671 polymorphism and AD was found under homozygous (DD vs dd), and dominant contrasts (DD + Dd vs dd), with OR = 0.47 (95% CI: 0.24, 0.92) and 0.46 (95% CI: 0.24, 0.88), respectively (p < 0.05). Whereas under allele (D vs d), heterozygous (Dd vs dd) and recessive contrasts (DD vs Dd + dd), no significant relationship was found. No significant relationship was found for rs1837253 or rs11466749. Serum TSLP levels were significantly higher in patients with AD, with the SMD = 1.45 (95% CI: 0.65, 2.25) (p < 0.05). Conclusions TSLP gene rs1898671 polymorphism was associated with AD, and TSLP levels were elevated in patients with AD. [ABSTRACT FROM AUTHOR]

Chloroquine is still used as a first-line treatment for uncomplicated Plasmodium vivax malaria in India and resistance to this therapy can act as a major hurdle for malaria elimination. It is difficult to monitor drug-efficacy and drug resistance through in vivo and in vitro studies in case of Plasmodium vivax so analysis of molecular markers serves as an important tool to track resistance. Molecular methods that are currently in use for detecting single nucleotide polymorphisms in resistant genes including Polymerase chain reaction (PCR), Realtime-Polymerase chain reaction require highly sophisticated labs and are time consuming. So, with this background the study has been designed to optimize Loop Mediated Isothermal Amplification Assay to detect single nucleotide polymorphisms in chloroquine resistance gene of Plasmodium vivax in field settings. Eighty-eight Plasmodium vivax positive samples were collected. Pvmdr1 gene was amplified for all the samples and sequenced. Obtained sequences were analyzed for the presence of single nucleotide polymorphisms in the target gene. Further Loop Mediated Isothermal Amplification Assay primer sets were designed for the target mutants and the assay was optimized. Clinical as well as analytical sensitivity and specificity for the assay was calculated. Double mutants with variations at T958M and F1076L were detected in 100% of the Plasmodium vivax clinical isolates with haplotype M958 Y976 Y1028 L1076. Designed primers for Loop Mediated Isothermal Amplification Assay successfully detected both the mutants (T958M and F1076L) in 100% of the isolates and do not show cross-reactivity with other strains. So, the assay was 100% sensitive and specific for detecting single nucleotide polymorphisms in the target Pvmdr1 gene. Limit of detection was found to be 0.9 copies/µl and lowest DNA template concentration detected by designed assay was 1.5 ng/µL. Observed prevalence of single nucleotide polymorphisms in Pvmdr 1 gene is indicating a beginning of trend towards chloroquine resistance in Plasmodium vivax. The present study optimized LAMP for detecting single nucleotide polymorphisms in Plasmodium vivax cases in field settings, thus would help in finding significant hubs of emerging chloroquine drug resistance and ultimately helping in the management of suitable antimalarial drug policy. [ABSTRACT FROM AUTHOR]

The Staphylococcus aureus (S. aureus) one of the important food borne pathogen from milk, which was investigated in this study. The isolates were screened for antimicrobial resistance, enterotoxin genes, biofilm formation, spa typing, coagulase gene polymorphism and accessory gene regulator types. The prevalence of S. aureus in milk samples was 34.4% (89/259). Methicillin resistant S. aureus (MRSA) was found at 27% (24/89) of the isolates, were classified as community acquired based on SCCmec typing. The 24.71% (22/89) isolates demonstrated multiple antimicrobial resistance (MAR) pattern. However, none of the isolates carried vancomycin and mupirocin resistance genes. The isolates were positive for sea and sed enterotoxin genes and exhibited high frequency of biofilm formation. The High-Resolution Melting and conventional spa typing revealed that the isolates had both animal and community-associated S. aureus clustered origins. Coagulase gene polymorphism and agr typing demonstrated variable genotypic patterns. The finding of this study establishes the prevalence of community associated, enterotoxigenic, biofilm forming and antimicrobial resistance among S. aureus from milk in Chennai city. This emphasizing a potential threat to public health which needs a continuous monitoring system and strategies to mitigate their spread across the food chain and achieve food safety. [ABSTRACT FROM AUTHOR]

Ethanol stress in Saccharomyces cerevisiae is a well-studied phenomenon, but pinpointing specific genes or polymorphisms governing ethanol tolerance remains a subject of ongoing debate. Naturally found in sugar-rich environments, this yeast has evolved to withstand high ethanol concentrations, primarily produced during fermentation in the presence of suitable oxygen or sugar levels. Originally a defense mechanism against competing microorganisms, yeast-produced ethanol is now a cornerstone of brewing and bioethanol industries, where customized yeasts require high ethanol resistance for economic viability. However, yeast strains exhibit varying degrees of ethanol tolerance, ranging from 8 to 20%, making the genetic architecture of this trait complex and challenging to decipher. In this study, we introduce a novel QTL mapping pipeline to investigate the genetic markers underlying ethanol tolerance in an industrial bioethanol S. cerevisiae strain. By calculating missense mutation frequency in an allele located in a prominent QTL region within a population of 1011 S. cerevisiae strains, we uncovered rare occurrences in gene IRA2. Following molecular validation, we confirmed the significant contribution of this gene to ethanol tolerance, particularly in concentrations exceeding 12% of ethanol. IRA2 pivotal role in stress tolerance due to its participation in the Ras-cAMP pathway was further supported by its involvement in other tolerance responses, including thermotolerance, low pH tolerance, and resistance to acetic acid. Understanding the genetic basis of ethanol stress in S. cerevisiae holds promise for developing robust yeast strains tailored for industrial applications. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) recurrence appears commonly after liver transplantation (LT), and it severely affected the long-term survival of patients. Previous studies have proved that Rap1A is involved in hepatocarcinogenesis and metastasis, and demonstrated the significant association between KRAS rs712 polymorphism and HCC. However, the relationship between KRAS rs712 polymorphism and HCC recurrence after LT remained unclear. A total of 93 HCC patients who underwent LT from March 2008 to Dec 2015 was analyzed. The genotypes of both donors and recipients had been confirmed as KRAS rs712. The independent risk factors that associated with HCC recurrence were investigated with univariate and multivariate logistic regression analysis. The recurrence-free (RFS) and overall survival (OS) were calculated with Cox regression analysis. The KRAS rs712 genotype frequencies were determined using the Χ2 test and the minor allele frequencies (MAFs) of KRAS rs712 genotypes were calculated by Hardy–Weinberg equilibrium. We found that the recipient KRAS rs712 polymorphism was significantly associated with HCC recurrence after LT. Moreover, the Milan criteria, microvascular invasion and recipient KRAS rs712 genotype were proved to be independent risk factors for HCC recurrence after LT. Patients with donor TG/TT genotypes had a significantly higher RFS and OS than TT genotype. The TNM stage, microvascular invasion, Milan criteria, treatment and recipient KRAS rs712 genotype were independent factors for the RFS of LT patients. Recipient KRAS rs712 polymorphism is associated with HCC recurrence after liver transplantation and plays as a promising bio-predictor of overall survival rate of HCC risks after hepatic transplantation. [ABSTRACT FROM AUTHOR]

The determinate growth habit of plants reduces the number of internodes and shortens the main stem by terminating the shoot apical meristem through a transition to inflorescence. Understanding the genetic basis of this habit can help optimize crop yield and cultivation technology for vegetable breeding. This study aimed to identify the determinate-2 (de-2) gene responsible for the determinate growth habit in the W-sk cucumber line. Termination of the main stem in the W-sk line occurred between 14 and 23 internodes, depending on cultivation conditions. Resequencing of the W-sk genome identified a novel SNP in the cucumber TERMINAL FLOWER1 (CsTFL1) gene, explaining the de-2 phenotype. This was verified with a CAPS-T marker cosegregation with determinate growth in the F2:3 population, and this polymorphism is unique among genotyped indeterminate cucumber cultivars or breeding lines. Crossing the W-sk line with the G421 line with the determinate (de) gene confirmed the allelism of both genes. An SNP in CsTFL1 in the W-sk line introduced a premature stop codon, resulting in the putative deletion of 13 amino acids, possibly causing determinate growth habit. Overall, this study provides insights into the genetic basis of cucumber plant growth architecture and advances in cucumber breeding. [ABSTRACT FROM AUTHOR]

Bartonella are vector-borne gram-negative facultative intracellular bacteria that can infect a wide spectrum of mammals, and are recognized as emerging human pathogens. This study aimed to investigate the prevalence and molecular characteristics of Bartonella infections in small mammals within the Qinghai Menyuan section of Qilian Mountain National Park, China. Small mammals were captured, and the liver, spleen and kidney were collected for Bartonella detection and identification using a combination of real-time PCR targeting the transfer-mRNA (ssrA) gene and followed by sequencing of the citrate synthase (gltA) gene. A total of 52 rodents were captured, and 36 rodents were positive for Bartonella, with a positivity rate of 69.23% (36/52). Bartonella was detected in Cricetulus longicaudatus, Microtus oeconomus, Mus musculus, and Ochotona cansus. The positivity rate was significantly different in the different habitats. Two Bartonella species were observed, including Bartonella grahamii and Bartonella heixiaziensis, and B. grahamii was the dominant epidemic strain in this area. Phylogenetic analysis showed that B. grahamii mainly clustered into two clusters, which were closely related to the Apodemus isolates from China and Japan and the local plateau pika isolates, respectively. In addition, genetic polymorphism analysis showed that B. grahamii had high genetic diversity, and its haplotype had certain regional differences and host specificity. Overall, high prevalence of Bartonella in small mammals in the Qinghai Menyuan section of Qilian Mountain National Park. B. grahamii is the dominant strain with high genetic diversity and potential pathogenicity to humans, and corresponding control measures should be considered. [ABSTRACT FROM AUTHOR]

This study aimed to explore the potential association between Endothelin type A receptor (EDNRA) genetic polymorphisms and susceptibility to large artery atherosclerotic stroke (LAA), as well as the involvement of inflammation mechanisms. We recruited Han Chinese patients with LAA and age- and sex-matched controls. The distribution of alleles and genotypes for 16 single nucleotide polymorphisms (SNPs) in EDNRA was analyzed using dominant, recessive, and co-dominant genetic models between cases and controls. We quantified the mRNA and protein levels of EDNRA and NLRP3 genes, and concentrations of inflammatory factors (TNFα, IL-1β, IL-6, IL-8, IL-10, IL-18, and CCL18) in peripheral blood samples randomly selected from cases and controls. We also investigated the relationship between these SNPs, gene expression patterns and inflammatory factor levels. A total of 428 LAA cases and 434 controls were enrolled in this study. The results showed that rs5343 TT genotype of EDNRA was significantly associated with an increased risk of LAA (OR = 3.243, 95%CI = 1.608–6.542, P = 0.001). It also demonstrated a significant upregulation level of NLRP3 as well as higher concentrations of IL-10, IL-18, and CCL-18 in cases compared to controls. Besides, we discovered that the EDNRA polymorphisms were linked to NLRP3, IL-6, IL-10, and IL-18 levels in cases. There existed a positive correlation between EDNRA transcription levels and both NLRP3 transcript levels (r = 0.437, p < 0.001) and IL-18 concentrations (r = 0.212, p < 0.001). EDNRA is linked to susceptibility of LAA. This association may be attributed to the NLRP3-mediated inflammatory pathway. [ABSTRACT FROM AUTHOR]

Background: Fat mass and obesity‐associated gene (FTO) genes rs9939609 is strongly associated with obesity and rs17817449 is an important and potential gene for obesity, have been well established. We aim to evaluate the relationship between FTO gene and overweight/obesity and confirm the influence of obesity on glucose and lipid metabolism parameters. Methods: We investigated 183 normal weight subjects and 193 individuals with overweight/obesity. Firstly, the effect of overweight/obesity on glucose and lipid metabolism parameters was analyzed. Then, the FTO genes rs9939609 and rs17817449 were counted to explore whether polymorphisms were associated with overweight/obesity and metabolic parameters. Results: Significant differences existed in glucose and lipid parameters between the group with overweight/obesity and control group. The rs9939609 and rs17817449 were strongly correlated with overweight/obesity. Haplotype analysis revealed that GA and GT haplotypes had 2.99 and 1.81 fold risk of overweight/obesity. FTO polymorphism also has effects on glucose and lipid metabolism parameters. Conclusions: There is a linkage imbalance between rs9939609 and rs17817449 in a Central China general population cohort, which also reflected the influence of FTO gene on the risk of overweight/obesity and total cholesterol (TC), triglyceride (TG), and high‐density lipoprotein (HDL) disorders. The new findings could provide new clues to predict obesity and metabolic diseases. [ABSTRACT FROM AUTHOR]

Background and objective: Genetic polymorphism studies in families and twins indicated the heritability of depression. However, the association between genes with genetic polymorphism and depression provides various findings and remains unclear. Therefore, we conducted a systematic review and meta-analysis to determine the genes with their polymorphism associated with the symptomatic depression known as major depressive disorder (MDD). Materials and methods: PubMed and Scopus were searched for relevant studies published before May 22, 2023 (1968–2023), and 62 were selected for this review. The study's bias risk was investigated using the Newcastle–Ottawa scale. Gene functional enrichment analysis was investigated for molecular function (MF) and biological process (BP) and pathways. A meta-analysis of the studied genes that were replicative in the same single nucleotide polymorphism was conducted using a random-effect model. Results: The 49 genes involved in MDD were studied and engaged in several pathways, such as tryptophan metabolism or dopaminergic and serotonergic synapses. Based on gene overlapping in MF and BP, 13 genes with polymorphisms were identified as related to MDD. Most of them were only studied once. Solute carrier family 6 member 4 (SLC6A4) overlapping between MF and BP and brain-derived neurotrophic factor (BDNF) as unique to BP were replicative studied and used in the meta-analysis. The polymorphism of SLC6A4 SS and LS genotypes increased the occurrence of MDD development but not significantly [odd ratio (OR) = 1.39; 95% confidence interval (CI) = 0.87–2.22; P = 0.16 and OR = 1.13; 95% CI = 0.84–1.53; P = 0.42, respectively]. A similar result was observed for BDNF rs6265 GG (OR = 1.26; 95% CI = 0.78–2.06; P = 0.35) and BDNF rs6265 AA genotypes (OR = 1.12; 95% CI = 0.77–1.64; P = 0.56). These studies indicated low bias and significant heterogeneity. Conclusion: At least 13 studied genes with polymorphisms were involved in MDD development according to MF and BP, but not significantly. These results suggest that MDD development risk factors might require genetic and other factors for interaction and induction. [ABSTRACT FROM AUTHOR]

ABSTRACT A major challenge in analysing single‐nucleotide polymorphism (SNP) genotype datasets is detecting and filtering errors that bias analyses and misinterpret ecological and evolutionary processes. Here, we present a comprehensive method to estimate and minimise genotyping error rates (deviations from the ‘true’ genotype) in any SNP datasets using triplicates (three repeats of the same sample) in a four‐step filtration pipeline. The approach involves: (1) SNP filtering by missing data; (2) SNP filtering by error rates; (3) sample filtering by missing data and (4) detection of recaptured individuals by using estimated SNP error rates. The modular pipeline is provided in an R script that allows customised adjustments. We demonstrate the applicability of the method using non‐invasive sampling from the Asiatic wild ass (Equus hemionus) population in Israel. We genotyped 756 samples using 625 SNPs, of which 255 were triplicates of 85 samples. The average SNP error rate, calculated based on the number of mismatching genotypes across triplicates before filtration, was 0.0034 and was reduced to 0.00174 following filtration. Evaluating genetic distance (GD) and relatedness (r) between triplicates before and after filtration (expected to be at the minimum and maximum respectively) showed a significant reduction in the average GD, from 58.1 to 25.3 (p = 0.0002) and a significant increase in relatedness, from r = 0.98 to r = 0.991 (p = 0.00587). We demonstrate how error rate estimation enhances recapture detection and improves genotype quality. [ABSTRACT FROM AUTHOR]

How phenotypic diversity originates and persists within populations are classic puzzles in evolutionary biology. While balanced polymorphisms segregate within many species, it remains rare for both the genetic basis and the selective forces to be known, leading to an incomplete understanding of many classes of traits under balancing selection. Here, we uncover the genetic architecture of a balanced sexual mimicry polymorphism and identify behavioral mechanisms that may be involved in its maintenance in the swordtail fish Xiphophorus birchmanni. We find that ∼40% of X. birchmanni males develop a "false gravid spot," a melanic pigmentation pattern that mimics the "pregnancy spot" associated with sexual maturity in female live-bearing fish. Using genome-wide association mapping, we detect a single intergenic region associated with variation in the false gravid spot phenotype, which is upstream of kitlga , a melanophore patterning gene. By performing long-read sequencing within and across populations, we identify complex structural rearrangements between alternate alleles at this locus. The false gravid spot haplotype drives increased allele-specific expression of kitlga , which provides a mechanistic explanation for the increased melanophore abundance that causes the spot. By studying social interactions in the laboratory and in nature, we find that males with the false gravid spot experience less aggression; however, they also receive increased attention from other males and are disdained by females. These behavioral interactions may contribute to the maintenance of this phenotypic polymorphism in natural populations. We speculate that structural variants affecting gene regulation may be an underappreciated driver of balanced polymorphisms across diverse species. [Display omitted] • The false gravid spot is a sexual mimicry polymorphism in swordtail fish • Non-coding structural variation increases expression of kitlga to drive the spot • Several lines of evidence suggest balancing selection maintains the polymorphism • The false gravid spot alters social interactions with both males and females The false gravid spot is a sexual mimicry polymorphism that allows males to mimic females. Dodge et al. link the phenotype to structural variation that increases expression of the nearby kitlga gene. The spot affects multiple social interactions with males and females, which may contribute to the persistence of this balanced polymorphism in nature. [ABSTRACT FROM AUTHOR]

Background and Aims Methods Results Conclusion Individuals with genetic polymorphisms in UGT1A1 exhibit bilirubin levels that belie their risk of liver disease (Gilbert's syndrome) but it is not known if this phenomenon extends to other common liver blood tests (LBTs).A genome‐wide association analysis of 10 LBTs was conducted using the UK biobank. Polygenic scores (PGS) were created from discordant loci (e.g. loci associated with the LBT but not associated with cirrhosis morbidity risk). Participants were assigned to a low, intermediate or high PGS for each LBT. A high PGS approximates Gilbert's syndrome (i.e. elevated LBT without an analogous increase in disease risk). The prognostic significance of an ‘elevated’ LBT—and how this differs by PGS—was assessed through competing risk survival analysis.This study included 157 005 and 166 871 participants for the discovery and validation phases, respectively. Elevated LBTs were more prevalent in the high versus low PGS group, yet the 10‐year risk of cirrhosis morbidity was comparable. For example, in the low PGS group, 4.3% had an elevated gamma‐glutamyltransferase (GGT) and the 10‐year risk of cirrhosis morbidity was .45%. Conversely, in the high PGS group, 21.2% had an elevated GGT and the 10‐year risk was .38%. Accordingly, the 10‐year risk of cirrhosis morbidity for individuals with an elevated GGT was markedly different in the low vs. high group (4.2% vs. 1.2%; p < .001). Similar results were apparent for Fibrosis‐4 index, total bilirubin, and platelet count.Variability in LBTs is influenced by genetic polymorphisms that have a neutral effect on disease risk. These findings have implications for interpreting elevated LBTs in clinical practice. [ABSTRACT FROM AUTHOR]

BackgroundAimSubjects and methodsResultsConclusionAlthough numerous mechanisms are involved in vitiligo pathogenesis, few studies correlate N-acetyltransferase 2 to this disease.To assess the N-acetyltransferase 2 (rs1799929) gene and its serum levels in vitiligo patients.In this case-control study, 65 vitiligo cases were compared to 65 age- and sex-matched healthy controls. Serum NAT2 levels and the NAT2 gene polymorphism (rs1799929) were evaluated using ELISA and real-time PCR, respectively.Serum N-acetyltransferase 2 levels were significantly lower in cases than in controls, 1.24 ± 0.31 vs. 2.01 ± 0.46 (p = 0.001). CC genotype was more dominant in controls (58.5%) than in cases (20%). TT and CT genotypes were more dominant in cases (30.8% and 49.2%) than in controls (13.8% and 27.7%), respectively (p = 0.001). The C allele was more prominent in controls (72.3%) than in cases (44.6%) while the T allele was more dominant in cases (55.4%) than in controls (27.7%) (p = 0.001). N-acetyltransferase 2 slow acetylator phenotype (TT genotype) was higher in cases (30.8%) than in controls (13.8%) and rapid acetylator phenotypes (CC and CT genotypes) were higher in controls (86.2%) than in cases (69.2%) (p = 0.035).Slow acetylator genotype (TT) of NAT2 gene (rs1799929) and low serum levels of NAT2 enzyme might play a role in the susceptibility and pathogenesis of vitiligo. [ABSTRACT FROM AUTHOR]

Background: There is no doubt that genetic factors have the potential to predict the therapeutic outcomes of antidepressants in patients with major depressive disorder (MDD). This study investigated the association between genetic variants involved in serotonin signaling and brain-derived neurotrophic factor (BDNF) with the response to escitalopram treatment in patients with MDD. We focused on examining the influence of 5-HTTLPR (ins/del), HTR2A rs9316233, BDNF rs962369, CYP2C19 and CYP2D6 on the clinical response to escitalopram. Methods: The patients were recruited from outpatient psychiatric clinics in Košice between 2020 and 2022. Patients received escitalopram for 12 weeks at a fixed dose of 10 mg daily. Clinical assessment was done at baseline and after 4, 8, and 12 weeks using the 21-item Hamilton Depression Rating Scale (HAMD-21). Results: At the end of week 12, 57 (65%) patients were defined as responders to escitalopram treatment, while 31 (35%) patients were non-responders. Genotyping revealed that carriers of the short allele (S) of 5-HTTLPR exhibit a significantly lower therapeutic response to escitalopram measured by HAMD-21 than the long allele (L) carriers (p = 0.01). Adjusting for CYP2C19 and CYP2D6 metabolizer genotypes did not modify the observed relationship between 5-HTTLPR and treatment response. No significant associations were found for HTR2A rs9316233 or BDNF rs962369 variants and the treatment response. Conclusions: These findings underscore the utility of 5-HTTLPR genotyping in guiding escitalopram therapy for MDD patients. Further research with larger cohorts is warranted to validate these results and elucidate additional genetic determinants of antidepressant efficacy. [ABSTRACT FROM AUTHOR]

Simple Summary: The genetic polymorphisms in the ovocalyxin-32 gene were studied in the present work with regard to egg quality traits in indigenous chicken populations. In the same investigation, based on exons 1 and 6, the frequencies of G/T and A/G SNPs regarding the Hardy–Weinberg equilibrium (HWE) and their role in egg quality were determined. The T allele of the G/T SNP in exon 1 was associated with thinner shells and lower shell strength, while the A/G SNP in exon 1 resulted in eternal eggs with thicker shells in AG and AA genotypes. Regarding this, the A/G SNP in exon 6 was able to enhance shell and yolk quality in AG genotypes. These SNPs could be considered candidate genetic markers for marker-assisted selection (MAS) focusing on egg quality improvement, which has additive and dominance genetic effects on phenotypic variation. This study sought to evaluate the genetic variations of the ovocalyxin-32 gene and its association with egg quality traits in indigenous chicken populations, focusing on exons 1 and 6. Genotype frequencies of SNPs (G/T and A/G) within these exons were assessed for their conformity to the Hardy–Weinberg equilibrium (HWE) across several strains. While most strains exhibited close adherence to HWE expectations, some like light-brown and gray strains indicated substantial discrepancies, particularly for the TT genotype, which points towards the possible effects of genetic drift as well as selection pressures. This study also analyzed the influence of such SNPs on egg quality parameters. A thinner eggshell, reduced shell weight, and decreased breaking strength were associated with the G/T SNP in exon 1, suggesting a likely negative effect on egg quality in T allele carriers. Conversely, the AG genotype displayed better performance in shell thickness, weight and egg weight in the A/G SNP in exon 1, whilst yolk height was best improved by the AA genotype compared to breaking strength. For instance, in exon 6, the A/G SNP enhanced the shell and yolk quality among AG genotypes, while the CC genotype resulted in better eggshell characteristics with enlarged yolks because the C/T SNP was linked. Nonetheless, there were no significant deviations from the HWE despite these associations, which suggested that most breeds had a stable genetic background. Further, considering SNPs' additive and dominant effects in this research, it was indicated that additive effects account for phenotypic expressions given by the G/T SNP located at exon 1. In contrast, significant additive and dominant effects were observed under the A/G SNP situated at the exon. Generally, it therefore could be concluded from this study that specific SNPs within the ovocalyxin-32 gene may act as good markers for marker-assisted selection (MAS) that can improve desired characteristics—such as those of egg quality—in indigenous chicken breeds. This study demonstrated that both additive and dominance effects must be taken into account when performing genetic analyses, thereby emphasizing the complexity of phenotypic variation caused by genetic mechanisms in native chicken races. [ABSTRACT FROM AUTHOR]

Hermansky–Pudlak syndrome (HPS) is a rare disease inherited in the autosomal recessive mode, including 11 clinical genetic subtypes. They are associated with impaired function of the BLOC protein complex (Biogenesis of Lysosome-related Organelles Complexes), and the subunits of the AP-3 complex (adaptor protein complex). Each has its own clinical features, but they are all characterized by albinism, bleeding disorder, and visual abnormalities. Eleven patients from eight unrelated families with an incoming diagnosis of albinism were examined and novel and previously described genetic variants in HPS1, HPS6, and BLOC1S6 genes (types HPS1, HPS6, and HPS9) were found. To determine the optimal therapy and recommendations for further follow up, it is necessary to consider the entire clinical spectrum and genetic polymorphism of the disease. An interdisciplinary approach, combined with the use of non-routine diagnostic techniques such as RNA analysis, is essential for achieving accurate diagnoses in certain complex cases. [ABSTRACT FROM AUTHOR]

Brain-derived neurotrophic factor (BDNF) is a potential biomarker of response to treatment in psychiatric disorders. As it plays a role in the pathophysiological development of schizophrenia and bipolar disorder, it is of interest to study its role in predicting therapeutic responses in both conditions. We carried out a systematic review of the literature, looking for differences in baseline BDNF levels and the Val66Met BDNF polymorphism in these disorders between responders and non-responders, and found information showing that the Val/Val genotype and higher baseline BDNF levels may be present in patients that respond successfully to pharmacological and non-pharmacological treatments. However, there is still limited evidence to support the role of the Val66Met polymorphism and baseline BDNF levels as predictors of treatment response. [ABSTRACT FROM AUTHOR]

Hypertensive disorders of pregnancy (HDP) are a great danger. A previous GWAS found a relationship between rs259983 of the ZNF831 gene and HDP, such as for chronic hypertension (CHTN) and preeclampsia (PE). We conducted the case-control study to determine the association between rs259983 of the ZNF831 gene and HDP in women with Gestational Diabetes Mellitus (GDM). For target genotyping, we developed primers and TaqMan probes. In analyzing the population, we did not manage to find a relationship between PE and rs259983 of the ZNF831 gene. Additional study of women with PE and PE superimposed on CHTN (SIPE) establishes an association between rs259983 of the ZNF831 gene only with SIPE. Carriers of CC genotypes have been discovered to have a 5.05 times higher risk of SIPE development in women with GDM. [ABSTRACT FROM AUTHOR]

Tacrolimus (Tc) is an immunosuppressant used in transplant patients, but its therapeutic range is narrow, making precise dosing essential. This study investigates the association of three single nucleotide polymorphisms (SNPs) (ABCB1 3435C>T, 1236C>T, 2677G>T/A) with Tc levels over time to gain better insights into their role in personalized medicine. We conducted the study over four distinct periods: 1–14 days, 15–30 days, 31–60 days, and beyond 60 days post-transplantation. The analysis included allele, genotype, haplotype, and diplotype frequencies of the three SNPs concerning Tc blood levels. Statistical significance was determined, and false discovery rate (PFDR) correction was applied where appropriate. Significant associations were found between the C (ABCB1 C1236T), A alleles (ABCB1 G2677T/A), the CAC haplotype and lower Tc levels. The CAC-TGT and TGT-TGT diplotypes significantly influence how patients metabolize the drug. The TGT haplotype and the AA genotype (ABCB1 G2677T/A) were associated with higher Tc levels, suggesting a long-term genetic influence. Genetic factors, specifically certain SNPs and diplotypes, significantly impact Tc blood levels, with their influence varying over time. [ABSTRACT FROM AUTHOR]

Borderline ovarian tumors (BOTS) are rare neoplasms of intermediate aggressiveness between cystadenomas and low-grade ovarian cancers (lgOvCa), which they share some molecular resemblances with. In contrast to the most frequent and well-described high-grade ovarian carcinomas (hgOvCa), the molecular background of BOTS and lgOvCa is less thoroughly characterized. Here, we aimed to analyze genetic variants in crucial tumor suppressors and oncogenes in BOTS (with or without the BRAF V600E mutation), lgOvCa, and hgOvCa in two gene panels using next-generation sequencing. Then, we verified the existence of selected polymorphisms by Sanger sequencing. Finally, Western blot analyses were carried out to check the impact of the selected polymorphisms on the expression of the corresponding proteins. Our study contributes to the molecular characterization of ovarian neoplasms, demonstrating divergent polymorphic patterns pointing to distinct signaling pathways engaged in their development. Certain mutations seem to play an important role in BOTS without the BRAF V600E variant (KRAS) and in lgOvCa (KRAS and NRAS), but not in hgOvCa. Additionally, based on multivariable regression analyses, potential biomarkers in BOTS (PARP1) and hgOvCa (FANCI, BRCA2, TSC2, FANCF) were identified. Noteworthy, for some of the analyzed genes, such as FANCI, FANCD2, and FANCI, FANCF, TSC2, the status of BRCA1/2 and TP53, respectively, turned out to be crucial. Our results shed new light on the similarities and differences in the polymorphic patterns between ovarian tumors of diverse aggressiveness. Furthermore, the biomarkers identified herein are of potential use as predictors of the prognosis and/or response to therapy. [ABSTRACT FROM AUTHOR]

Evolutionary biology aims to explain the diversity seen in nature. Evolutionary theory provides frameworks to understand how simple polymorphisms or continuous variation are maintained, but phenotypes inherited as discrete suites of quantitative traits are difficult to fit into this framework. Supergenes have been proposed as a solution to this problem—if causal genes are co-located, they can be inherited as if a single gene, thus bridging the gap between simple polymorphisms and continuous traits. We develop models to ask: how are critical supergenes for maintaining phenotypic diversity? In our simplest model, without explicit genetic architectures, three alternative reproductive morphs are maintained in many of the parameter combinations we evaluated. For these same parameter values, models with demographic stochasticity, recombination and mutation (but without explicit genetic architecture) maintained only two of these three morphs, with stochasticity determining which morphs persisted. With explicit genetic architectures, regardless of whether causal loci were co-located in a supergene or distributed randomly, this stochasticity in which morphs are maintained was reduced. Even when phenotypic variation was lost, genetic diversity was maintained. Altogether, categorical traits with polygenic bases exhibited similar evolutionary dynamics to those determined by supergenes. Our work suggests that supergenes are not the only answer to the puzzle of how discrete polygenic phenotypic variation is maintained. [ABSTRACT FROM AUTHOR]

Methylenetetrahydrofolate reductase (MTHFR) plays a crucial role in regulating one-carbon metabolism. Polymorphisms within the MTHFR gene have been found to increase the risk of breast cancer in different populations. In this study, we evaluated the association of polymorphisms of the MTHFR gene (rs1801133 and rs1801131) with the risk of breast cancer in the Bangladeshi population. This case‒control study included 202 breast cancer patients and 104 healthy controls. After the organic extraction of DNA, genotyping was performed via the PCR-RFLP method. Sanger sequencing was performed to validate the RFLP data. Statistical analyses were performed to evaluate the associations of the polymorphisms. Different computational tools were used to predict the structural and functional consequences of the SNPs. Our study revealed that the MTHFR gene polymorphism rs1801131 is associated with an increased risk of developing breast cancer (p < 0.001, OR = 3.85, 95% CI = 2.06–7.25 for the AC genotype and p < 0.001, OR = 7.82, 95% CI = 2.69–22.05 for the CC genotype). An association was also observed in the dominant model (AC + CC) (p < 0.001, OR = 4.19, 95% CI = 2.28–7.78). For rs1801131, premenopausal status was significantly associated with breast cancer risk (p < 0.001). For rs1801133, no significant association was found with breast cancer risk (p > 0.05, OR = 1.57, 95% CI = 0.90–2.74 for the CT genotype; p > 0.05, OR = 1.35, 95% CI = 0.36–4.92 for the TT genotype). Computational analyses predicted rs1801131 to be tolerated and rs1801133 to be deleterious. Structural analyses demonstrated no significant changes in protein structure but revealed alterations in neighboring interactions according to both bond distances and angles. In conclusion, rs1801131 but not rs1801133 is significantly associated with breast cancer risk in the Bangladeshi population. Moreover, in silico analyses demonstrated changes in the interaction pattern of polymorphic residues with adjacent amino acids. [ABSTRACT FROM AUTHOR]

The nucleotide excision repair (NER) system is one of the main ways to protect organisms from DNA damage caused by endogenous and exogenous carcinogens. NER deficiency increases genome mutations, chromosomal aberrations, and cancer viability. However, the genetic association between Wilms tumor and NER pathway gene polymorphisms needs to be further validated. We assessed the associations between 19 NER gene polymorphisms and Wilms tumor susceptibility in 416 cases and 936 controls from East China via the TaqMan method. We found that xeroderma pigmentosum group D (XPD) rs238406 and rs13181 significantly decreased the risk of Wilms tumor [adjusted odds ratio (OR) = 0.59, 95% confidence interval (CI) = 0.46–0.75, p <.0001; adjusted OR = 0.63, 95% CI = 0.44–0.89, p = .009, respectively]. Furthermore, the rs751402 and rs2296147 polymorphisms in the xeroderma pigmentosum group G (XPG) gene were significantly correlated with an increased risk for Wilms tumor (adjusted OR = 1.47, 95% CI = 1.03–2.09, p = .034; adjusted OR = 2.14, 95% CI = 1.29–3.56, p = .003, respectively). Expression quantitative trait loci (eQTL) analysis revealed that these four polymorphisms may affect the expression of genes that are adjacent to XPD and XPG. Our study provides evidence that XPD and XPG gene polymorphisms are associated with Wilms tumor risk. Nonetheless, these findings should be confirmed in a larger sample size. [ABSTRACT FROM AUTHOR]

Background: In the domain of forensic science, the application of kinship identification and mixture deconvolution techniques are of critical importance, providing robust scientific evidence for the resolution of complex cases. Microhaplotypes, as the emerging class of genetic markers, have been widely studied in forensics due to their high polymorphisms and excellent stability. Results and discussion: In this research, a novel and high-efficient panel integrating 33 microhaplotype loci along with a sex-determining locus was developed by the next generation sequencing technology. In addition, we also assessed its forensic utility and delved into its capacity for kinship analysis and mixture deconvolution. The average effective number of alleles (Ae) of the 33 microhaplotype loci in the Guizhou Han population was 6.06, and the Ae values of 30 loci were greater than 5. The cumulative power of discrimination and cumulative power of exclusion values of the novel panel in the Guizhou Han population were 1-5.6 × 10− 43 and 1-1.6 × 10− 15, respectively. In the simulated kinship analysis, the panel could effectively distinguish between parent-child, full-sibling, half-sibling, grandfather-grandson, aunt-nephew and unrelated individuals, but uncertainty rates clearly increased when distinguishing between first cousins and unrelated individuals. For the mixtures, the novel panel had demonstrated excellent performance in estimating the number of contributors of mixtures with 1 to 5 contributors in combination with the machine learning methods. Conclusions: In summary, we have developed a small and high-efficient panel for forensic genetics, which could provide novel insights into forensic complex kinships testing and mixture deconvolution. [ABSTRACT FROM AUTHOR]

Subacute sclerosing panencephalitis (SSPE) is a progressive and catastrophic neurodegenerative disorder due to persistent infection with the aberrant measles virus in the brain. The exact etiology of SSPE is still unknown, and early diagnosis remains a challenge, especially with the atypical presentations. The pathogenesis of SSPE involves a complex interplay between viral factors and immunological response of the host. The presenting review demonstrates an extensive glimpse of the immuno‐genetics of SSPE, exploring the single‐nucleotide polymorphisms (SNPs), genetic risk factors and immune responses that influence susceptibility and disease progression. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion X‐linked dystonia‐parkinsonism (XDP), a neurodegenerative movement disorder endemic to the Philippines, is primarily investigated in patients from Panay Island and the Greater Manila area. However, individuals residing in geographically distant regions may exhibit different clinical or genetic characteristics compared to those documented in earlier reports.The aim was to investigate the relationship of XDP clinical features in a Mindanao cohort with modifiers of age at onset (AAO) variability and utilization of a previously reported AAO model.We investigated clinical and genetic features in 27 XDP patients from southern Mindanao. In all patients, we genotyped the 4 polymorphisms linked to AAO.The XDP‐relevant hexanucleotide repeat number significantly correlated with AAO in the 27 patients and explained about 68% of AAO variability. There is no statistical difference between the predicted and actual AAO.The AAO model may provide reliable predictions by employing the effect of XDP genetic modifiers of AAO variability. [ABSTRACT FROM AUTHOR]

Atorvastatin is a widely prescribed cholesterol‐lowering drug that inhibits 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase to reduce lipid levels. This study aimed to establish a population pharmacokinetic and pharmacodynamic model for atorvastatin in Chinese lung transplant recipients (LTRs), particularly those using voriconazole (VOR) and with different genotypes. It evaluated precise dosing regimens and analyzed the correlation between atorvastatin exposure and clinical outcomes. A nonlinear mixed‐effects model was used for the population pharmacokinetic/pharmacodynamic (PK/PD) analysis. A one‐compartment population PK model was developed, incorporating VOR, SLCO2A1 rs76906503, and SLC22A8 rs2187383 to assess apparent clearance and volume of distribution. LDL‐C was modeled as a biomarker to evaluate atorvastatin efficacy. A Monte Carlo simulation was conducted to assess various dosing schemes and the effects of different covariates on achieving the target LDL concentration. The correlation between atorvastatin exposure and clinical outcomes was also evaluated. Results indicated that the average probability of target attainment for optimal dosing regimens across various covariate results exceeded 45.8%. Dosages of 10, 20, and 40 mg were deemed suitable for LTRs. A lower dose was recommended for LTRs taking VOR or with mutant‐type genotypes to avoid overexposure and adverse reactions. The population PK/PD model offers valuable guidance for evaluating atorvastatin dosing regimens in clinical settings, particularly for LTRs using VOR and those with different genotypes. [ABSTRACT FROM AUTHOR]

Background: Tibetan highlanders have adapted to hypoxic environments through genetic mechanisms that avoid hemoglobin concentration increases and prevent polycythemia. Recently, sex differences in hemoglobin dynamics with age have been reported among Tibetan highlanders living in Tsarang. Additionally, concerns have been raised that dietary changes associated with modernization may increase the risk of polycythemia and lifestyle-related diseases among Tibetan highlanders. However, the relationship between genetic polymorphisms and the risk of lifestyle-related diseases in Tibetan highlanders has been investigated in only a few regions. This study aims to elucidate whether polymorphisms in genes related to hypoxic adaptation are associated with the incidence of lifestyle-related diseases and polycythemia and whether these polymorphisms affect hemoglobin dynamics in the residents of Tsarang, Mustang, Nepal. Methods: Health checkup data from individuals living in Tsarang in Mustang District, Nepal, collected in 2017, were used to determine the prevalence of obesity, hypertension, diabetes, hypoxemia, and polycythemia. DNA was extracted from whole-blood samples, and data for the single-nucleotide polymorphisms (SNPs) rs13419896 (EPAS1), rs12619696 (EPAS1), and rs2790859 (EGLN1) were obtained using real-time PCR. The health checkup data were statistically analyzed to determine the associations of these diseases with polymorphisms in genes related to hypoxic adaptation. Results: A total of 168 participants, comprising 78 males and 90 females, were included in the final analysis. In terms of the prevalence of each disease, only the prevalence of polycythemia significantly differed between sexes (p < 0.01). Additionally, among the three analyzed SNPs, significant sex differences in genotype frequency were observed for rs13419896 and rs2790859. For rs2790859 in females, Tibetan highlanders with the adaptive genotype had a significantly lower incidence of polycythemia (p < 0.01) and significantly lower hemoglobin concentrations (p < 0.01). Conclusions: This study revealed that there are sex differences in the genotype frequency of gene-related hypoxic adaptations among the residents of Tsarang. The findings also suggested that the rs2790859 polymorphism might be involved in the recent incidence of polycythemia among Tsarang residents. If the frequency of non-Tibetan genotypes increases due to intermixing with other populations in the Mustang District, polycythemia may emerge as a modern disease. It is essential to continue investigating the health status of Mustang residents to elucidate various aspects of hypoxic adaptation and disease susceptibility. [ABSTRACT FROM AUTHOR]

Vicia sativa L., commonly known as the common vetch, is an annual, self-pollinating legume used primarily as fodder both by livestock and wildlife. Additionally, it contributes to environmental balance through nitrogen fixation and the improvement of soil properties. The phenotypic, genetic, and metabolite variability among four advanced lines (BK45, BK29, BK23, BK27) and two commercial varieties (M-6900, BI-65) of V. sativa were evaluated in order to be used for future breeding programs aimed at producing genetically improved varieties. BK45 was the most promising line due to its high genetic polymorphism, but also because it exhibited a significant amount of seed production and high seed quality based on its metabolomics profile. A stepwise multiple regression analysis (MRA) revealed a relationship between SCoT alleles, seed, and biomass yield. Additionally, several statistically significant marker bands linked to metabolites were found using the SCoT marker analysis. Hence, data assessed via MRA may be helpful in marker-assisted breeding programs. Finally, the two commercial varieties can be further exploited in breeding programs due to their high genetic diversity. [ABSTRACT FROM AUTHOR]

Introduction: Cisplatin is a widely used chemotherapeutic agent prescribed to treat solid tumors. However, its clinical application is limited because of cisplatininduced nephrotoxicity. A known complication of cisplatin is acute kidney injury (AKI). Deletion polymorphisms of GSTM1 and GSTT1, members of the glutathione S-transferase family, are common in humans and are presumed to be associated with various kidney diseases. However, the specific roles and mechanisms of GSTM1 and GSTT1 in cisplatin induced AKI remain unclear. Methods: To investigate the roles of GSTM1 and GSTT1 in cisplatin-induced AKI, we generated GSTM1 and GSTT1 knockout mice using CRISPR-Cas9 technology and assessed their kidney function under normal physiological conditions and cisplatin treatment. Using ELISA kits, we measured the levels of oxidative DNA and protein damage, along with MDA, SOD, GSH, and the GSH/GSSG ratio in wild-type and GSTM1/GSTT1 knockout mice following cisplatin treatment. Additionally, oxidative stress levels and the expression of ferroptosis-related proteins in kidney tissues were examined through Western blotting, qPCR, immunohistochemistry, and immunofluorescence techniques. Results: Here, we found that GSTT1 and GSTM1 were downregulated in the renal tubular cells of AKI patients and cisplatin-treated mice. Compared with WT mice, Gstm1/Gstt1-DKO mice were phenotypically normal but developed more severe kidney dysfunction and exhibited increased ROS levels and severe ferroptosis after injecting cisplatin. Discussion: Our study revealed that GSTM1 and GSTT1 can protect renal tubular cells against cisplatin-induced nephrotoxicity and ferroptosis, and genetic screening for GSTM1 and GSTT1 polymorphisms can help determine a standard cisplatin dose for cancer patients undergoing chemotherapy. [ABSTRACT FROM AUTHOR]