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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]

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]

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.

Background: Dilated cardiomyopathy (DCM) is a major cause of heart failure and heart transplantation. Recently, some studies have reported that the autoimmune response in myocardial cells might be related to the pathogenesis of DCM. The CD247 gene has been previously found to be involved in autoimmune disease. Therefore, our study aimed to clarify the hypothesis that there is a certain linkage between polymorphisms of the CD247 gene and the triggering of DCM risk. Methods: In the present study, two single nucleotide polymorphisms (SNPs) of the CD247 gene, rs12141731 and rs858543, were genotyped by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) in 355 DCM patients and 404 age- and sex-matched controls. Results: Pearson's chi-squared test for the CD247 gene revealed that SNP rs858543 (p = 0.001, OR = 0.72, 95% CI = (0.588–0.882), but not SNP rs12141731, was associated with DCM in the Chinese Han population. Haplotype analysis revealed that the CC haplotype was associated with increased DCM susceptibility, while CT was a protective haplotype. Cox multivariate survival analysis indicated that the rs858543 TT genotype (HR: 0.608, 95% CI = 0.402–0.921, p = 0.019) was an independent multivariate predictor for longer overall survival in DCM patients. CD247 mRNA expression levels were significantly decreased in DCM patients (p = 0.02). Conclusions: Our study suggested that a polymorphism in the CD247 gene may be a risk factor for DCM in the Chinese Han population. Trial registration: ChiCTR2000029701. [ABSTRACT FROM AUTHOR]

Zanthoxylum is a versatile economic tree species utilized for its spice, seasoning, oil, medicinal, and industrial raw material applications, and it has a lengthy history of cultivation and domestication in China. This has led to the development of numerous cultivars. However, the phenomenon of mixed cultivars and confusing names has significantly obstructed the effective utilization of Zanthoxylum resources and industrial development. Consequently, conducting genetic diversity studies and cultivar identification on Zanthoxylum are crucial. This research analyzed the genetic traits of 80 Zanthoxylum cultivars using simple sequence repeat (SSR) and inter-Primer Binding Site (iPBS) molecular markers, leading to the creation of a DNA fingerprint. This study identified 206 and 127 alleles with 32 SSR markers and 10 iPBS markers, respectively, yielding an average of 6.4 and 12.7 alleles (Na) per marker. The average polymorphism information content (PIC) for the SSR and iPBS markers was 0.710 and 0.281, respectively. The genetic similarity coefficients for the 80 Zanthoxylum accessions ranged from 0.0947 to 0.9868 and from 0.2206 to 1.0000, with mean values of 0.3864 and 0.5215, respectively, indicating substantial genetic diversity. Cluster analysis, corroborated by principal coordinate analysis (PCoA), categorized these accessions into three primary groups. Analysis of the genetic differentiation among the three Zanthoxylum (Z. bungeanum, Z. armatum, and Z. piperitum) populations using SSR markers revealed a mean genetic differentiation coefficient (Fst) of 0.335 and a gene flow (Nm) of 0.629, suggesting significant genetic divergence among the populations. Molecular variance analysis (AMOVA) indicated that 65% of the genetic variation occurred within individuals, while 35% occurred among populations. Bayesian model-based analysis of population genetic structure divided all materials into two groups. The combined PI and PIsibs value of the 32 SSR markers were 4.265 × 10− 27 and 1.282 × 10− 11, respectively, showing strong fingerprinting power. DNA fingerprints of the 80 cultivars were established using eight pairs of SSR primers, each assigned a unique numerical code. In summary, while both markers were effective at assessing the genetic diversity and relationships of Zanthoxylum species, SSR markers demonstrated superior polymorphism and cultivar discrimination compared to iPBS markers. These findings offer a scientific foundation for the conservation and sustainable use of Zanthoxylum species. [ABSTRACT FROM AUTHOR]

The role of CYP2E1 in oxidation is essential for its effects on meat quality. This study used 200 Indonesian sheep (Ovis aries) to determine the SNP g allele frequencies. g. 50658168 T>C of CYP2E1 gene located in 3´-UTR region and their genetic association with lamb quality traits, including carcass characteristics, retail cut carcass, physicochemical lamb, fatty acid, cholesterol, flavor and odor, and mineral content. Further, the level of CYP2E1 mRNA and CYP2E1 protein expression in muscle were determined and correlated with lamb quality traits. CYP2E1 gene polymorphisms were identified using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) analysis. The CYP2E1 mRNA expression levels in phenotypically divergent sheep populations were analyzed using Quantitative Real Time-PCR (qRT-PCR). Immunohistochemistry (IHC) and hematoxylin-eosin (HE) staining analysis used three samples each in the high and low lamb quality groups based on pH value and tenderness. An association study of CYP2E1 gene polymorphisms was performed using General Linear Model (GLM) analysis. The genetic association between the CC, CT, and TT genotypes at the SNP g. 50658168 T>C CYP2E1 gene and lamb quality traits were significant (P<0.05), including carcass characteristics, retail cut carcass, fatty acid, cholesterol, flavor, and odor. Lambs with the CT genotype had a higher mRNA and protein expression in high lamb quality traits. The highest CYP2E1 protein expression was localized in the longissimus dorsi. The group sample with high lamb quality had a higher area and perimeter of muscle cells. CYP2E1 can be used as a genetic marker for selecting sheep with high meat quality. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori (H. pylori) virulence factors, particularly the cagA and vacA genotypes, play important roles in the pathogenic process of gastrointestinal disease. Methods: The cagA and vacA genotypes of 87 H. pylori strains were determined by PCR and sequencing. The EPIYA and CM motif patterns were analyzed and related to clinical outcomes. We examined the associations between the virulence genes of H. pylori and gastrointestinal diseases in Shandong, and the results were analyzed via the chi-square test and logistic regression model. Results: Overall, 76 (87.36%) of the strains carried the East Asian-type CagA, with the ABD types being the most prevalent (90.79%). However, no significant differences were observed among the different clinical outcomes. The analysis of CagA sequence types revealed 8 distinct types, encompassing 250 EPIYA motifs, including 4 types of EPIYA or EPIYA-like sequences. Additionally, 28 CM motifs were identified, with the most prevalent patterns being E (66.67%), D (16.09%), and W-W (5.75%). Notably, a significant association was discovered between strains with GC and the CM motif pattern D (P < 0.01). With respect to the vacA genotypes, the strains were identified as s1, s2, m1, m2, i1, i2, d1, d2, c1, and c2 in 87 (100%), 0 (0), 26 (29.89%), 61 (70.11%), 73 (83.91%), 14 (16.09%), 76 (87.36%), 11 (12.64%), 18 (20.69%), and 69 (79.31%), respectively. Specifically, the vacA m1 and c1 genotypes presented a significantly greater prevalence in strains from GC compared to CG (P < 0.05). Following adjustment for age and sex, the vacA c1 genotype demonstrated a notable association with GC (OR = 5.174; 95% CI, 1.402–20.810; P = 0.012). This association was both independent of and more pronounced than the correlations between vacA m1 and GC. Conclusions: CagA proteins possessing CM motif pattern D were more frequently observed in patients with GC (P < 0.01), implying a potentially higher virulence of CM motif pattern D than the other CM motif patterns. Moreover, a strong positive association was identified between the vacA c1 genotype and GC, indicating that the vacA c1 genotype is a robust risk indicator for GC among male patients aged ≥55 years in Shandong. [ABSTRACT FROM AUTHOR]

ABSTRACT Sugarcane (Saccharum spp. hybrids) are complex polyploid and aneuploid interspecific hybrids with 110–130 chromosomes. A traditional sugarcane breeding cycle takes 13–15 years and involves multiple years and locations testing of yield. To identify molecular markers associated with yield‐related traits, the LCP 85‐384 cultivar and its mapping population of 263 self‐progenies were planted in two randomly replicated field plots. The mapping population was genotyped with amplified fragment length polymorphism (AFLP), simple sequence repeats (SSR) and target region amplification polymorphism (TRAP) markers. Data on plant height, stalk number, stalk diameter and stalk weight were collected. A large variation was observed for each trait. A genome‐wide association study (GWAS) was conducted using mixed linear model (MLM), generalized linear model (GLM) and single marker regression (SMR) programmes of TASSEL 5 and FarmCPU of GAPIT 3. A total of 64 yield trait‐associated alleles were identified, including 11 for stalk number, 36 for stalk weight, 21 for stalk diameter and 5 for plant height. Of the 64 alleles, seven were linked to two traits and one to three traits. Genomic prediction (GP) was also performed by cross‐prediction with five models, namely, ridge regression best linear unbiased prediction (rrBLUP), Bayesian ridge regression (BRR), Bayesian A (BA), Bayesian B (BB), and Bayesian least absolute shrinkage and selection operator (BL). Prediction accuracy (r value) reached 0.40 for plant height, 0.36 for stalk number, 0.44 for stalk diameter and 0.54 for stalk weight with the standard errors from 0.009 to 0.012. Once verified, these markers will be a valuable tool to aid in the selection of yield‐related traits in sugarcane improvement programmes. [ABSTRACT FROM AUTHOR]

Objective: This meta-analysis aims to clarify the association between the TNF-α -308G > A and − 238G > A polymorphisms and lung cancer risk. Method: A comprehensive search was conducted for relevant articles across databases such as PubMed, Google Scholar, Web of Science, EMBASE, and CNKI, up to September 25, 2023. Lung cancer risk was assessed by calculating odds ratios (ORs) and their 95% confidence intervals (CIs). The Z-test was used to determine the significance of combined ORs, with P < 0.05 considered statistically significant. All analyses were performed using Comprehensive Meta-Analysis (CMA) 2.0 software. Results: The analysis included 19 case-control studies with 3,838 cases and 5,306 controls for the TNF-α -308G > A polymorphism, along with 10 studies comprising 2,427 cases and 2,357 controls for the − 238G > A polymorphism. The − 308G > A polymorphism showed no significant overall relationships, though in the Asian subgroup, the A allele was significantly reduced compared to G (OR: 0.831, p = 0.028) and the AA genotype showed significant reductions versus GG (OR: 0.571, p = 0.021), with no significant correlation in Caucasians. In non-small cell lung cancer (NSCLC), the A allele was associated with increased risk compared to G (OR: 1.131, p = 0.049). For the − 238G > A polymorphism, the AA genotype significantly increased risk compared to GG (OR: 3.171, p = 0.014), while showing a protective effect in Caucasians (OR: 0.120, p = 0.024) and a heightened risk in Asians (OR: 7.990, p = 0.007). In small cell lung cancer (SCLC), the A allele conferred protective effects, whereas NSCLC showed increased risk for the AA genotype (OR: 11.375, p = 0.002). Conclusion: The − 308G > A polymorphism has no significant overall relationships but suggests a protective role of the A allele in the Asian subgroup. Conversely, the − 238G > A polymorphism presents a complex risk profile, increasing lung cancer likelihood in Asians while protecting Caucasians. Notably, the AA genotype significantly raises risk for NSCLC, indicating its potential as a risk factor. [ABSTRACT FROM AUTHOR]

Background: Bronchial asthma (BA) is a chronic inflammatory disorder identified by different endotypes and phenotypes. Chemokine receptor 3 (CCR3) is one of the essential chemokine receptors that have a crucial role in asthma development by activating the migration of eosinophils through eotaxin production. We aimed to determine asthma prevalence among school children and to investigate the association between CCR3-T51C gene polymorphisms and the symptom-based clinical asthma phenotypes. Methods: This study employed a hybrid design, conducted at a single center in Egypt from 2020 to 2021, to explore the relationship between asthma, its clinical phenotypes, and the CCR3-T51C gene polymorphism. Initially, a cross-sectional analysis was performed, utilizing a modified version of the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire to determine the prevalence of asthma in a cohort of 60 children, who presented with diverse clinical phenotypes, alongside 100 healthy controls. Subsequently, in the case–control phase of the study, we focused on examining the association between asthma (and its clinical phenotypes) and the CCR3-T51C gene polymorphism. For both groups, serum immunoglobulin E (IgE) levels and eosinophil counts were assessed, and the genotypes and alleles of the CCR3-T51C gene polymorphism were identified using the polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) technique. Results: A total of 600 children aged (6 to 16 years old) were enrolled. Out of these, 72 children (12%) were diagnosed with bronchial asthma in the basic education schools in El Manzala City, Egypt. Also, 72 (12%) of the studied children had wheezes, and 48 (8%) had night cough. Children with asthma had significantly higher relative eosinophil count and serum IgE levels than the control group. In terms of CCR3-T51C genotypes analysis, the TT genotype was the most prevalent in both patient and control groups, with 63.3% and 64%, respectively, but the difference was not statistically significant (P > 0.05). Also, there were no significant associations between CCR3-T51C genotypes and laboratory biomarkers among cough, wheezy, and cough and wheezy groups, except for the CT genotype in the cough group that had a lower eosinophil count than the wheezy group (P = 0.04). Conclusion: Asthma affects 12% of the school-aged children. The CCR3-T51C genotype or allelic polymorphism frequency did not differ between asthmatics and controls; however, the TT genotype was more frequent in asthmatic children. Eosinophil count, serum IgE and gene polymorphism of CCR3-T51C appeared similar among different asthmatic phenotypes. [ABSTRACT FROM AUTHOR]

Objective: This work aimed to investigate the potential correlation between chromosomal polymorphisms and various reproductive abnormalities. Methods: We examined 21,916 patients affected by infertility who sought care at the Department of Reproductive Medicine, Affiliated Hospital of Shandong Second Medical University between January 2018 and December 2022. A total of 2227 individuals identified as chromosomal polymorphism carriers constituted the polymorphism group, and 2245 individuals with normal chromosome karyotypes were randomly selected to form a control group. Clinical manifestations, histories of spontaneous miscarriage, abnormal reproductive developments, fetal abnormalities, and male sperm quality anomalies were statistically compared between these two groups. Results: Of the 21,916 patients analyzed, 2227 displayed chromosomal polymorphism, representing a 10.16% detection rate. Amongst the male patients, 1622 out of 10,827 exhibited polymorphisms (14.98%), whereas 605 out of 11,089 females showed polymorphisms (5.46%). Female carriers in the polymorphism group, showed statistically significant increased rates of spontaneous abortion (29.75% vs. 18.54%), fetal anomalies (1.32% vs. 0.81%), and uterine abnormalities compared with the control group (1.32% vs. 0.81%). Male carriers in the polymorphism group had higher rates of spontaneous abortion in partners (22.87% vs. 10.37%), fetal anomalies (1.97% vs. 0.25%), compromised sperm quality (41.74% vs. 7.18%), testicular underdevelopment (2.28% vs. 0.92%), and hypogonadotropic hypogonadism (0.62% vs. 0.37%) compared with the control group. Conclusion: Chromosomal polymorphisms may have a certain negative effect on reproductive irregularities, including spontaneous abortions, fetal anomalies, and reduced sperm quality in males. Their clinical effects deserve further investigation. [ABSTRACT FROM AUTHOR]

Backgrounds: Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for hematological malignancies, it can be associated with relevant post-transplant complications. Several reports have shown that polymorphisms in immune system genes are correlated with the development of post-transplant complications. Within this context, this work focuses on identifying novel polymorphisms in cytokine genes and developing predictive models to anticipate the risk of developing graft-versus-host disease (GVHD), transplantation-related mortality (TRM), relapse and overall survival (OS). Methods: Our group developed a 132-cytokine gene panel which was tested in 90 patients who underwent an HLA-identical sibling-donor allo-HSCT. Bayesian logistic regression (BLR) models were used to select the most relevant variables. Based on the cut-off points selected for each model, patients were classified as being at high or low-risk for each of the post-transplant complications (aGVHD II-IV, aGVHD III-IV, cGVHD, mod-sev cGVHD, TRM, relapse and OS). Results: A total of 737 polymorphisms were selected from the custom panel genes. Of these, 41 polymorphisms were included in the predictive models in 30 cytokine genes were selected (17 interleukins and 13 chemokines). Of these polymorphisms, 5 (12.2%) were located in coding regions, and 36 (87.8%) in noncoding regions. All models had a statistical significance of p<0.0001. Conclusion: Overall, genomic polymorphisms in cytokine genes make it possible to anticipate the development all complications studied following allo-HSCT and, consequently, to optimize the clinical management of patients. [ABSTRACT FROM AUTHOR]

Background: Increased hemoglobin concentrations may increase the risk of varicose veins. However, the underlying relationship between them was not yet understood. Methods: Mendelian randomization (MR) analysis was performed to investigate causal effect between mean corpuscular hemoglobin concentration (MCHC, exposure factor) and varicose veins (outcome). Afterward, sensitivity analysis was used to ensure the reliability of MR analysis results. Then Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of SNPs were performed. A search tool for recurring instances of neighbouring genes (STRING) database was used to construct a protein-protein interaction (PPI) network. Results: Therefore, the inverse-variance weighted (IVW) results showed there existed a causal relationship between MCHC and varicose veins (p = 0.0026), with MCHC serving as a significant risk factor. (odd ratio [OR] = 1.2321). In addition, the validity of the results of the forward MR analysis was verified by sensitivity analysis. Further, a PPI network of 92 single-nucleotide polymorphisms (SNPs) which used for forward MR analysis related genes was constructed. And they were found to be closely associated with the peroxisome proliferator-activated receptor (PPAR) signalling pathway and cellular response to external stimulus by enrichment analysis. In addition, we clarified that the effect of varicose veins on MCHC was minimal by reverse MR analysis, suggesting that the results of forward MR analysis were not disturbed by reverse results. Conclusion: This study found a causal relationship between varicose veins and MCHC, which provided strong evidence for the effect of hemoglobin on varicose veins, and a new thought for the diagnosis and prevention of varicose veins in the future. [ABSTRACT FROM AUTHOR]

Annamocarya sinensis (Dode) Leroy, a relict plant from the Tertiary period, is a member of Annamocarya genus in the Juglandaceae family. Despite its wide distribution in Guangxi Province, the habitats of this species had become fragmented and isolated, causing it facing deterioration. For protecting this endangered species, it is crucial to understand its status in the wild and genetic diversity. In this study, 216 A. sinensis accessions from 18 populations in Guangxi were examined using Start Codon Target Polymorphism (SCoT) markers for PCR amplification, genetic diversity, and population structure analysis. Out of the 20 SCoT primers used, 222 sites were amplified, with 185 being polymorphic (PPB of 83.33%). Polymorphic information content values ranged from 0.4380 to 0.4999, Nei's genetic diversity index ranging from 0.1573 to 0.2503, and Shannon diversity index ranged from 0.1583 to 0.3812. Through AMOVA analysis, the total genetic diversity and genetic diversity within populations was calculated out as 0.3271 and 0.1542 respectively, the genetic differentiation coefficient between populations was 0.5286, with a gene flow 0.4458. Cluster analysis categorized A. sinensis germplasm into three groups, while population structure analysis divided all accessions into three ancestral sources with 19.91% showing mixed ancestral origins. No significant correlation was observed between genetic and geographical distance on the Mentel test (r = 0.07348, p = 0.7468). Overall, A. sinensis displays a relatively rich genetic diversity at the species level, albeit with a fairly uniform genetic background and high genetic differentiation. This study provides a crucial basis for the conservation and innovative use of A. sinensis germplasm resources. [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 Methods Results Conclusions This study investigates the mutational profile of the KIT gene in primary and metastatic melanomas, highlighting the significance of genetic heterogeneity.This research is a retrospective cohort that includes formalin‐fixed and paraffin‐embedded melanoma samples obtained from Hospital São Paulo, Brazil, between the years of 1996 and 2010. The research encompasses primary melanomas of the superficial spreading (SSM) and acral lentiginous (AL) subtypes and their metastases, using next‐generation sequencing to explore genetic heterogeneity.Despite losing 57 samples due to quality issues, 27 samples from 20 patients were analyzed, revealing a nearly equal distribution between AL and SSM subtypes. Both histological subtypes revealed KIT gene variants, including previously undescribed variants and polymorphisms, emphasizing the role of such mutations in melanoma pathogenesis and the potential for targeted therapies. Tumor heterogeneity was also observed in both histological subtypes.The study underscores the complexity of melanoma, driven by diverse mutational landscapes within and across tumors and advocates for personalized treatment approaches based on detailed molecular profiling. Despite limitations like sample size, this research lays the groundwork for further investigation into melanoma's genetic intricacies and therapeutic vulnerabilities. [ABSTRACT FROM AUTHOR]

Over time, researchers have accumulated significant evidence indicating that vitamin D deficiency not only impacts skeletal health but also contributes to the development and progression of various diseases, including cancer, diabetes, and cardiovascular conditions. The risk of low serum 1, 25(OH)2D3 level ultimately directs the way to morbidity, the beginning of new diseases, and numerous infections. Infections are the first entity that affects those with vitamin D deficiency. The common infection is urinary tract infection (UTI), and its relationship with vitamin D deficiency or insufficiency remains controversial. This infection affects both men and women, but comparatively, women are more prone to this infection because of the short length of the urethra, which makes an easy entry for the bacteria. The low level of serum vitamin D increases the risk of UTIs in children. Recurrent UTIs are one of the major weaknesses in women; if left untreated, they progress to appallingly serious conditions like kidney dysfunction, liver damage, etc. Hence improving the vitamin D status may help to improve the immune system, thus making it more resistant to infections. In this review, we have focused on examining whether vitamin D deficiency and insufficiency are the causes of UTIs and the association between them in women and children. We have also described the connection between vitamin D deficiency and insufficiency with UTIs and additional nanotechnology- based treatment strategies. [ABSTRACT FROM AUTHOR]

The recent emergence of chronic wasting disease (CWD) in Europe has become a new public health risk for monitoring of wild and farmed cervids. This disease, due to prions, has proliferated in North America in a contagious manner. In several mammalian species, polymorphisms in the prion protein gene (PRNP) play a crucial role in the susceptibility to prions and their spread. To obtain a reliable picture of the distribution of PRNP polymorphisms in the two most common cervid species in France, we sequenced the open reading frame (ORF) of this gene in 2114 animals, 1116 roe deer (Capreolus capreolus) and 998 red deer (Cervus elaphus). Selection criteria such as historical origin, spatial distribution and sex ratio have been integrated to establish this sample collection. Except for one heterozygous animal with a non-synonymous mutation at codon 37 (G37A), all the 1116 French roe deer were monomorphic. Red deer showed greater variation with two non-synonymous substitutions (T98A; Q226E), three synonymous substitutions (codons 21, 78 and 136) and a new 24pb deletion (Δ69-77). We found significant regional variations between French regions in the frequency of the identified substitutions. After cloning of the PRNP ORF from animals presenting multiple non-synonymous polymorphisms, we identified six haplotypes and obtained a total of twelve genotypes. As in other European countries, we highlighted the apparent homogeneity of PRNP in the French roe deer and the existence of a greater diversity in the red deer. These results were in line with European phylogeographic studies on these two species. [ABSTRACT FROM AUTHOR]

Objective: Tuberculosis (TB) is the leading cause of mortality worldwide. Previous studies have reported that TB susceptibility can be caused by vitamin D deficiency, which is affected by polymorphisms in the vitamin D receptor (VDR) gene. However, these results have been inconsistent. Therefore, we performed a meta-analysis to investigate the association between VDR polymorphisms and TB susceptibility. Methods: We systematically searched for relevant literature in PubMed, Embase, and Medline databases through December 31st, 2022. Inclusion and exclusion criteria were made to ensure that HIV-negative population is the targeted subjects. The pooled odds ratio (OR) and 95% confidence interval (CI) were then used to assess the strength of the association, and the quality of the included articles was evaluated using the Newcastle-Ottawa Scale. Potential sources of heterogeneity were evaluated based on subgroup and meta-regression analyses. Results: In our meta-analysis, we found that the FokI polymorphism in the VDR gene was associated with increased TB susceptibility in the allele and recessive genotype models (OR f vs. F = 1.235, 95%CI: 1.035-1.475; OR ff vs. Ff + FF = 1.317, 95%CI: 1.00-1.727. Further subgroup analysis based on ethnicity demonstrated the association with the risk of TB in all genotype models of the FokI polymorphism for Han population. Meta-regression analysis also indicated that ethnicity could be a potential source of heterogeneity in the FokI and BsmI polymorphisms in the VDR gene. However, publication year was another source of heterogeneity for the TaqI polymorphism. Conclusion: In summary, the FokI polymorphism in the VDR gene was found to increase the risk of TB in the HIV-negative population, both overall and in Asian populations. The findings presented in this paper could provide clues for preventing TB from the perspective of vitamin D supplementation, which is a controversial topic in the field of medicine and health. [ABSTRACT FROM AUTHOR]

Our knowledge of human evolutionary history has been greatly advanced by paleogenomics. Since the 2020s, the study of ancient DNA has increasingly focused on reconstructing the recent past. However, the accuracy of paleogenomic methods in resolving questions of historical and archaeological importance amidst the increased demographic complexity and decreased genetic differentiation remains an open question. We evaluated the performance and behavior of two commonly used methods, qpAdm and the f 3-statistic, on admixture inference under a diversity of demographic models and data conditions. We performed two complementary simulation approaches—firstly exploring a wide demographic parameter space under four simple demographic models of varying complexities and configurations using branch-length data from two chromosomes—and secondly, we analyzed a model of Eurasian history composed of 59 populations using whole-genome data modified with ancient DNA conditions such as SNP ascertainment, data missingness, and pseudohaploidization. We observe that population differentiation is the primary factor driving qpAdm performance. Notably, while complex gene flow histories influence which models are classified as plausible, they do not reduce overall performance. Under conditions reflective of the historical period, qpAdm most frequently identifies the true model as plausible among a small candidate set of closely related populations. To increase the utility for resolving fine-scaled hypotheses, we provide a heuristic for further distinguishing between candidate models that incorporates qpAdm model P -values and f 3-statistics. Finally, we demonstrate a significant performance increase for qpAdm using whole-genome branch-length f 2-statistics, highlighting the potential for improved demographic inference that could be achieved with future advancements in f -statistic estimations. [ABSTRACT FROM AUTHOR]

Background Given that obesity and insulin resistance play key roles in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and the connection between leptin and these metabolic diseases, the association between NAFLD and a leptin receptor gene (LEPR) polymorphism was examined. Methods In this genetic case-control association study, 144 biopsy-proven NAFLD patients and 144 controls were genotyped for the LEPR gene Gln223Arg (rs1137101) polymorphism using the polymerase chain reaction–restriction fragment length polymorphism method. Results The distributions of genotypes and alleles of Gln223Arg variant were in accordance with the Hardy-Weinberg equilibrium in the study groups (P >.05). Multivariate logistic regression analysis showed that the LEPR Gln223Arg Arg/Arg genotype was an independent risk factor for NAFLD; the Arg/Arg genotype, compared with the Gln/Gln genotype, was associated with a 2.09-fold increased risk for NAFLD (P =.036, odds ratio = 2.09 [95% CI = 1.31-5.95]). Conclusions We found that the LEPR Gln223Arg Arg/Arg genotype was independently associated with a more than 2-fold rise in biopsy-proven NAFLD risk. Our findings, however, need to be corroborated by further studies. [ABSTRACT FROM AUTHOR]

Background & Objective: Hypovitaminosis D has shown to be linked with T2DM development and control in numerous studies. The association of SNPs in genes related to VitD metabolism with T2DM has not been sufficiently studied. Consequently, our aim in the present study was to explore the association between genetic variants in genes connected with VitD, mainly a SNP in GC (rs1155563), a SNP in DHCR7 (rs12785878) and a SNP in CYP2R1 (rs10500804) with glycaemic parameters in females with T2DM in Saudi Arabia. Methods: The cross-sectional study included 149 females (age 38-52 years) with T2DM from Jeddah, Saudi Arabia (September 2022-March 2023). Blood was extracted from the participants for biochemical tests including measuring VitD [25(OH)D] concentration, parameters of glycaemia (HbA1c, insulin, fasting glucose and insulin sensitivity indices including HOMA2-IR and HOMA2-%β), and for genomic DNA isolation. Sanger DNA sequencing was used to screen for VitD genetic polymorphisms (rs1155563, rs12785878 and rs10500804). Results: Minor allele frequency for rs1155563C, rs12785878T and rs10500804G was 0.21, 0.23 and 0.37, respectively. Levels of 25(OH)D and glycaemic parameters as well did not show any significant difference between the genotypes of each SNP. Conclusion: This study showed lack of association of rs1155563 in GC, rs12785878 in DHCR7 and rs10500804 in CYP2R1 with VitD level primarily and with glycaemic parameters secondarily. Additional research is required to explore further other VitD genetic polymorphisms influencing T2DM which might lead consequently to genetically-based personalized management for T2DM. [ABSTRACT FROM AUTHOR]

Objective Idiopathic inflammatory myopathies (IIM) are a heterogeneous and life-threatening group of diseases; in particular, anti-melanoma differentiation-associated gene 5 antibody positive DM (MDA5+ DM) is reportedly strongly associated with high mortality rate. Tacrolimus (TAC) provides an excellent therapeutic option, but the trough concentration (Cmin)–outcome relationship remains unexplored. This study was undertaken to identify optimal Cmin and individualized dose based on CYP3A5 genotype for IIM patients. Methods A total of 134 IIM patients with 467 Cmin were enrolled. We examined the relationship between TAC Cmin and relapses. The receiver operating characteristic analysis was used to confirm the optimal Cmin. Analyses of factors influencing Cmin were conducted. The dose requirement based on CYP3A5 genotype was confirmed. Results TAC Cmin is strongly associated with relapses. The optimal cutoff values were 5.30, 5.85, 4.85 and 5.35 ng/ml for acute, subacute, chronic and all-phase IIM patients (P   =  0.001, 0.013, 0.002 and <0.001, respectively), as well as 5.35, 5.85, 5.55 and 5.85 ng/ml for acute, subacute, chronic and all-phase MDA5+ DM patients (P   =  0.007, 0.001, 0.036 and <0.001, respectively). CYP3A5 genotype was one of the significant factors influencing TAC Cmin. CYP3A5 expressers required 0.059 mg/kg/day to attain the target Cmin, while nonexpressers required 0.046 mg/kg/day (P   =  0.019). Conclusion TAC treatment may elicit favorable outcome in patients with IIM and MDA5+ DM when Cmin exceeded 5.35 and 5.85 ng/ml, which is crucial to a lower relapse rate. The individualized dose based on the CYP3A5 genotype provides a reference for TAC personalized therapy in IIM. [ABSTRACT FROM AUTHOR]

Investigative genetic genealogy (IGG) has emerged as a highly effective tool for tying a forensic DNA sample to an identity. While much of the attention paid to IGG has focused on cases where the DNA is from an unknown suspect, IGG has also been used to help close hundreds of unidentified human remains (UHR) cases. Genome‐wide single‐nucleotide polymorphism (SNP) genotype data can be obtained from forensic samples using microarray genotyping or whole‐genome sequencing (WGS) with protocols optimized for degraded DNA. After bioinformatic processing, the SNP data can be uploaded to public GG databases that allow law enforcement usage, where it can be compared with other users' data to find distant relatives. A genetic genealogist can then build the family trees of the relatives to narrow down the identity of the source of the forensic DNA sample. To date, 367 UHR identifications using IGG have been publicly announced. The same IGG techniques developed and refined for UHR cases have significant potential for disaster victim identification, where DNA is often extremely compromised, and close family references may not be available. This paper reviews the laboratory, bioinformatic, and genealogical techniques used in IGG for UHR cases and presents three case studies that demonstrate how IGG is assisting with remains identification. [ABSTRACT FROM AUTHOR]

Introduction: Genetic factors play an important role in the etiopathogenesis of autism spectrum disorder (ASD). The Pogo Transposable Element with ZNF Domain protein (POGZ) gene (MIM*614787) has been reported to be one of the most frequently mutated genes associated with ASD. This study aims to analyze the exonic regions of the POGZ gene in individuals diagnosed with non-syndromic ASD. Methods: Fifty-one non-syndromic cases diagnosed with ASD according to the DSM-V diagnostic criteria, aged 2-18 years, were included in the study. The healthy control group consisted of 50 children of similar age groups without neurodevelopmental problems. Amplicons produced using deep intronic primers covering the mRNA-encoded regions of the POGZ gene from at least 50 base pairs were sequenced by Next Generation Sequencing Analysis. Results: No pathogenic or likely pathogenic variants reported in open-access databases (ClinVar, HGMD, etc.) were detected in the case group. In the ASD and healthy control groups, rs113396244, rs11204811, rs779479223, rs772352054, rs3831142, rs112072925, rs227453 and rs142860188 variants were determined. The rs3831142, rs112072925, rs2274535, rs142860188 variants were found statistically significant in the ASD group. The distribution of the cases with detected single nucleotide polymorphisms (SNPs) according to gender was not statistically significant. Conclusion: The variants identified as statistically significant within the patient group are situated in regions that encompass both the HP1-ZNF and DDE domains of the protein. Given the crucial role that the DDE domain plays, particularly in fetal brain development and neurogenesis, these four variants may potentially possess modifying and/or predisposing effects in the context of ASD. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder that impacts women before reaching menopause. In addition to notable features (irregular ovulation, elevated androgen levels, and the existence of numerous ovarian cysts), individuals with PCOS frequently encounter diverse metabolic, cardiovascular, and psychological conditions. The onset of PCOS is influenced by a combination of factors, and various genetic variations are believed to play a significant role in its progression. The objective of the current study was to explore the link between genetic variations in the candidate genes thyroid-adenoma-associated (THADA) gene and insulin receptor (INSR) and susceptibility to developing PCOS. We conducted an extensive search across various databases, including Google Scholar, PubMed, Science Direct, Scopus, and EMBASE, to compile relevant case-control studies and literature reviews for subsequent statistical analysis. In the present study, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist was followed, a guideline for Systematic Reviews and Meta-Analysis. While a previous meta-analysis explored the correlation between INSR rs1799817 and THADA rs13429458 and their association with susceptibility to PCOS, our current study did not integrate any findings from these prior investigations. Our research encompassed articles published between 2017 and 2023, and we employed MetaGenyo software to assess the collected data. Statistical power analysis was performed using G*Power 3.1 software. Odds ratios and their corresponding 95% confidence intervals were calculated for each genetic model. Fifteen studies that met the criteria were analyzed. Out of these, ten studies, involving 1,189 cases and 1,005 controls, examined the INSR rs1799817 gene polymorphism, while five studies, including 783 cases and 553 controls, investigated the THADA rs13429458 gene polymorphism. The meta-analysis results indicated that there was no statistically significant association between the INSR rs1799817 gene polymorphism and the risk of PCOS (p>0.05). In contrast, the THADA rs13429458 gene polymorphism showed a significant association with PCOS risk under the over-dominant model (p<0.05). The present meta-analysis demonstrated a notable association between the THADA rs13429458 gene polymorphism and the likelihood of developing PCOS. Further rigorous studies with expanded sample sizes and diverse ethnic representation will be important to comprehensively evaluate and validate these findings. [ABSTRACT FROM AUTHOR]

Background: Genetic polymorphisms of molecules are known to cause individual differences in the therapeutic efficacy of anticancer drugs. However, to date, germline mutations (but not somatic mutations) for anticancer drugs have not been adequately studied. The objective of this study was to investigate the association between germline polymorphisms of gemcitabine metabolic and transporter genes with carbohydrate antigen 19‐9 (CA 19‐9) response (decrease ≥50% from the pretreatment level at 8 weeks) and overall survival (OS) in patients with metastatic pancreatic cancer who receive gemcitabine‐based chemotherapy. Methods: This multicenter, prospective, observational study enrolled patients with metastatic pancreatic cancer patients who were receiving gemcitabine monotherapy or gemcitabine plus nanoparticle albumin‐bound paclitaxel combination chemotherapy. Thirteen polymorphisms that may be involved in gemcitabine responsiveness were genotyped, and univariate and multivariate logistic regression analyses were used to determine the association of these genotypes with CA 19‐9 response and OS. The significance level was set at 5%. Results: In total, 180 patients from 11 hospitals in Japan were registered, and 159 patients whose CA 19‐9 response could be assessed were included in the final analysis. Patients who had a CA 19‐9 response had significantly longer OS (372 vs. 241 days; p =.007). RRM1 2464A>G and RRM2 175T>G polymorphisms suggested a weak association with CA 19‐9 response and OS, but it was not statistically significant. COX‐2 −765G>C polymorphism did not significantly correlate with CA 19‐9 response but was significantly associated with OS (hazard ratio, 2.031; p =.019). Conclusions: Genetic polymorphisms from the pharmacokinetics of gemcitabine did not indicate a significant association with efficacy, but COX‐2 polymorphisms involved in tumor cell proliferation might affect OS. This study investigated the association between germline polymorphisms of gemcitabine metabolic and transporter genes and carbohydrate 19‐9 response and overall survival in patients with metastatic pancreatic cancer who were receiving gemcitabine‐based chemotherapy. Germline polymorphisms of the metabolic pathway and transporter genes in gemcitabine were not significantly associated with efficacy, but COX‐2 polymorphisms were associated with overall survival. [ABSTRACT FROM AUTHOR]

Anthocyanin-rich 'blue maize' is emerging as a superfood worldwide. Traditionally maize grains lack anthocyanin, thus warrant attention from the breeders. Here, full-length 4467 bp Anthocyanin1 (A1) gene was sequenced among five wild-type (A1) and five mutant (a1) maize inbreds. A set of 21 InDel-based markers was developed and used for studying allelic diversity among 28 wild-type and 20 mutant-type inbreds. The major allele frequency ranging 0.417–0.938 had polymorphism information content ranging 0.110–0.574. Phylogenetic analysis categorized 48 inbreds into two clusters and 47 haplotypes. The epimerase domain of the Nicotinamide adenine dinucleotide (NAD)-dependent epimerase family was identified as a major functional domain of 357 amino acid long dihydroflavonol-4-reductase protein. Two polymorphisms viz. , (i) G (wild-type) to T (mutant-type) single nucleotide polymorphism (SNP) in the promoter, and (ii) 712 bp or 7 bp InDel (insertion in mutant) in exon-4 differentiated the wild-type and mutant allele. Two breeder-friendly PCR-based codominant markers viz., a gene-based allele-specific Cleaved amplified polymorphic sequence (CAPS) marker (MGU-A1–1053) and a functional InDel-based marker (MGU-A1–2840), were developed and validated among 48 inbreds and four F 2 populations. These markers can be effectively utilized in genomics-assisted breeding for blue maize that holds great potential to address malnutrition through a sustainable and cost-effective approach. [Display omitted] • An SNP (G/T) & an Indel (7 bp/712 bp) differentiated wild and mutant alleles of A1. • Two breeder-friendly gene-based markers for A1 were developed. • Both the markers were validated in 48 diverse inbreds and four F 2 populations. • 21 A1 -based markers revealed 47 haplotypes among diverse maize inbreds. • The study assumes great significance in molecular breeding for blue maize hybrids. [ABSTRACT FROM AUTHOR]

Aim: To explore the potential association between the KLF14 rs4731702 polymorphism and metabolic syndrome traits among patients diagnosed with type 1 diabetes (T1D). Methods: The study group included 350 patients with T1D and 250 healthy control subjects. The analysis focused on the genotyping of KLF14 rs4731702 single nucleotide polymorphism (SNP), as well as evaluating serum concentrations of inflammatory markers, blood pressure, lipid profiles, and the quantitative status of CD4 + CD25highFOXP3+ T cells. Results: Patients with T1D carrying the T allele of KLF14 rs4731702 SNP had higher high‐density lipoprotein cholesterol, lower low‐density lipoprotein cholesterol, as well as lower glycated haemoglobin and serum concentration of proinflammatory markers than C allele carriers. They also developed hypertension less often than carriers of the C allele. The analysis of CD4 + CD25highFOXP3+ regulatory T‐cell status based on KLF14 genotype showed that, in T1D patients, those with the TT genotype had the highest frequency of these cells compared to carriers of the CC and CT genotypes. Conclusion: Our study suggests that the T allele of the KLF14 rs4731702 SNP might confer a protective effect against the development of obesity, hypertension, dyslipidaemia, and chronic inflammatory state in patients diagnosed with T1D. [ABSTRACT FROM AUTHOR]

Human genetic variation (polymorphisms) in genes coding proteins involved in the absorption, distribution, metabolism, and elimination (ADME) of drugs can have a strong effect on drug exposure and downstream efficacy and safety outcomes. Vamorolone, a dissociative steroidal anti‐inflammatory drug for treating Duchenne muscular dystrophy (DMD), primarily undergoes oxidation by CYP3A4 and CYP3A5 and glucuronidation by UDP‐glucuronosyltransferases. This work assesses the pharmacokinetics (PKs) of vamorolone and sources of interindividual variability (IIV) in 81 steroid‐naïve boys with DMD aged 4 to <7 years old considering the genetic polymorphisms of CYPS3A4 (CYP3A4*22, CYP3A4*1B), CYP3A5 (CYP3A5*3), and UGT1A1 (UGT1A1*60) utilizing population PK modeling. A one‐compartment model with zero‐order absorption (Tk0, duration of absorption), linear clearance (CL/F), and volume (V/F) describes the plasma PK data for boys with DMD receiving a wide range of vamorolone doses (0.25‐6 mg/kg/day). The typical CL/F and V/F values of vamorolone were 35.8 L/h and 119 L, with modest IIV. The population Tk0 was 3.14 h yielding an average zero‐order absorption rate (k0) of 1.16 mg/kg/h with similar absorption kinetics across subjects at the same vamorolone dose (i.e., no IIV on Tk0). The covariate analysis showed that none of the genetic covariates had any significant impact on the PKs of vamorolone in boys with DMD. Thus, the PKs of vamorolone is very consistent in these young boys with DMD. [ABSTRACT FROM AUTHOR]

Background: Febrile urinary tract infections (UTIs) are among the most severe bacterial infections in infants, in which a subset of patients develops complications. Identifying infants at risk of recurrent infections or kidney damage based on clinical signs is challenging. Previous observations suggest that genetic factors influence UTI outcomes and could serve as predictors of disease severity. In this study, we conducted a nationwide survey of infant genotypes to develop a strategy for infection management based on individual genetic risk. Our aims were to identify genetic susceptibility variants for renal scarring (RS) and genetic host factors predisposing to dilating vesicoureteral reflux (VUR) and recurrent UTIs. Methods: To assess genetic susceptibility, we collected and analyzed DNA from blood using exome genotyping. Disease-associated genetic variants were identified through bioinformatics analysis, including allelic frequency tests and odds ratio calculations. Kidney involvement was defined using dimercaptosuccinic acid (DMSA) scintigraphy. Results: In this investigation, a cohort comprising 1087 infants presenting with their first episode of febrile UTI was included. Among this cohort, a subset of 137 infants who underwent DMSA scanning was subjected to gene association analysis. Remarkable genetic distinctions were observed between patients with RS and those exhibiting resolved kidney involvement. Notably, the genetic signature indicative of renal scarring prominently featured mitochondrial genes. Conclusions: In this nationwide study of genetic susceptibility to RS after febrile UTIs in infancy, we identified a profile dominated by mitochondrial polymorphisms. This profile can serve as a predictor of future complications, including RS and recurrent UTIs. [ABSTRACT FROM AUTHOR]

Experimental evolution was carried out to investigate the adaptive responses of extremotolerant fungi to a stressful environment. For 12 cultivation cycles, the halotolerant black yeasts Aureobasidium pullulans and Aureobasidium subglaciale were grown at high NaCl or glycerol concentrations, and the halophilic basidiomycete Wallemia ichthyophaga was grown close to its lower NaCl growth limit. All evolved Aureobasidium spp. accelerated their growth at low water activity. Whole genomes of the evolved strains were sequenced. No aneuploidies were detected in any of the genomes, contrary to previous studies on experimental evolution at high salinity with other species. However, several hundred single‐nucleotide polymorphisms were identified compared with the genomes of the progenitor strains. Two functional groups of genes were overrepresented among the genes presumably affected by single‐nucleotide polymorphisms: voltage‐gated potassium channels in A. pullulans at high NaCl concentration, and hydrophobins in W. ichthyophaga at low NaCl concentration. Both groups of genes were previously associated with adaptation to high salinity. Finally, most evolved Aureobasidium spp. strains were found to have increased intracellular and decreased extracellular glycerol concentrations at high salinity, suggesting that the strains have optimised their management of glycerol, their most important compatible solute. Experimental evolution therefore not only confirmed the role of potassium transport, glycerol management, and cell wall in survival at low water activity, but also demonstrated that fungi from extreme environments can further improve their growth rates under constant extreme conditions in a relatively short time and without large scale genomic rearrangements. [ABSTRACT FROM AUTHOR]

Geological events can have a major effect on the genetic structure and differentiation of fish populations. The relative importance of key geological events on the distribution and genetic structure of endemic fish of the genus Discogobio in the Yunnan–Guizhou Plateau has not yet been evaluated. Studies of the phylogeography of Discogobio fishes could provide insights into spatial and temporal changes in their population size, dispersal history, and extent of geographical isolation, and the data acquired in such studies can be used to aid their conservation. Here, we used single‐nucleotide polymorphisms (SNP) to characterize the phylogeography of Discogobio fishes. Our analysis supports the endemicity of Discogobio. However, Discogobio samples from different regions contained multiple ancestral components, including admixed and diversified genetic components. This might stem from polymorphism of the ancestors themselves or the infiltration of genes caused by hybridization between Discogobio species. We estimated that the most recent common ancestor (MRCA) of Discogobio fish in the Central Yunnan Basin was approximately 4.63–3.83 million years ago (Ma). We also inferred that the evolution of Discogobio in the Central Yunnan Basin was closely related to the expansion and contraction of the lake basin around 2.59–0.13 Ma. We proposed measures that could be implemented to conserve remaining populations and their corresponding habitats to prevent further declines and preserve the biodiversity of this unique genus. [ABSTRACT FROM AUTHOR]

This study compared blood pressure (BP) and heart rate variability (HRV) values considering the angiotensin-converting enzyme (ACE) polymorphisms and physical activity (PA) level. Participants were stratified according to their ACE polymorphism and PA level. Polymerase chain reaction (PCR) was used to detect polymorphisms and PA level was assessed by questionnaire. Participants had their BP measured by an oscillometer and the HRV rerded using a heart monitor. Participants grouped by polymorphism II showed higher values of root mean square successive difference when compared to individuals with DD polymorphism. "Highly active", compared to "active", individuals exhibited a lower diastolic BP. There was no statistically significant difference in the behavior of the dependent variables between the different PA levels within each polymorphism. Polymorphism II attenuated parasympathetic activity in cardiac autonomic modulation and the "highly active" group displayed lower values of diastolic BP. PA level did not affect any variable when polymorphisms were considered. [ABSTRACT FROM AUTHOR]

The inhibin alpha (INHA) serves as a marker for the number of fully developed ovarian follicles and plays a crucial role in regulating the secretion of pituitary FSH (follicle-stimulating hormone) and the frequency of ovulation. This study aims to examine the effect of INHA gene polymorphisms on the litter size of thin-tailed sheep. Detection of single nucleotide polymorphisms (SNPs) in the INHA gene was performed using PCR and DNA sequencing techniques. A total of 45 ewes were included in the study. Three SNPs were identified: g.236311141G>C, g.236311367G>A, and g.236311368G>A. Further investigation of the g.236311367G > A variant revealed that individuals with the GA genotype had a significantly higher litter size than those with the AA or GG genotype (p<0.05). SNPs at positions g.236311141G/C and g.236311368G/A were non-synonymous mutations resulting in amino acid changes p.A225P and V301I, respectively. Our results suggest that g.236311367G>A loci may serve as a potential molecular marker for improving the litter size trait in thin-tailed sheep. [ABSTRACT FROM AUTHOR]

Background: Twin studies revealed that genetic effects play a role in hand eczema (HE), but the responsible genetic factors are unknown. Objectives: To identify and characterise genetic loci associated with HE and to provide insight into the genetic overlap between HE and atopic dermatitis (AD). Methods: We used questionnaire‐derived and genotype data from the European population‐based Lifelines cohort and biobank. We performed a discovery genome‐wide association study (GWAS) of HE (2879 cases and 16 249 controls) and of AD (1706 cases and 17 190 controls). We replicated our findings in an independent Lifelines sample for HE (1188 cases and 6431 controls) and AD (757 cases and 6747 controls). We conducted several post‐GWAS analyses and performed genetic correlation analyses between our HE results and independent AD data. Results: The two‐step GWAS of HE, regardless of adjusting for AD, identified one independent locus 20q13.33, likely driven by a number of causal single‐nucleotide polymorphisms. For the AD GWAS, we replicated a known stop‐gained rs61816761 at locus 1q21.3 (FLG, FLGAS1). We found a strong genetic correlation (p < 0.01) between HE and AD (rg = 0.65), regardless of adjusting for AD (rg = 0.63). Conclusions: Locus 20q13.33 is associated with HE, and there is a large genetic overlap between HE and AD. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine the optimal irrigation needs of six popular Egyptian bread wheat (Triticum aestivum L.) cultivars and to establish baseline effect of reduced irrigation on yield. The varieties included were Sids1, Sids14, Sakha94, Sakha95, Gemmiza12, and Shandawee1. The experiment was conducted at two different locations, Nubaria and Sids Agricultural Research Stations, Egypt over two consecutive seasons, 2020–2021 and 2021–2022. There was a reduction in yield with the decrease in the number of irrigations. However, several cultivars performed better for yield and other traits with one less irrigation than the current irrigation practices in the region. Therefore, the study may help revise irrigation recommendations. Overall, the cultivars Sakha95, Sids1, and Sids14 were taller and had more kernels per spike, higher seed index, and greater grain yield under reduced irrigations and showed the best drought tolerance index. The tested bread wheat cultivars were genotyped using Inter-Retrotransposon Amplified Polymorphism (IRAP) and Start Codon Targeted (SCoT) markers which showed relation among the cultivars. Among the two types of markers, IRAP was better than SCoT markers for reliability and robustness. Among the six cultivars, 58% of the IRAP markers detected polymorphism as compared to 38% with SCoT markers. The two wheat cultivars Sids1 and Sids14, which performed better for important agronomic traits under water stress conditions, could be used as donors for the national wheat breeding program for drought tolerance. [ABSTRACT FROM AUTHOR]

This study evaluated the genetic diversity of 253 taro (Colocasia esculenta (L.) Schott) germplasm accessions collected in Vietnam at the molecular level using 20 Simple Sequence Repeat (SSR) markers. High genetic diversity in the taro germplasm accessions were detected with 100% polymorphic SSR loci, and 89 alleles were obtained at the 20 SSR loci with an average of 4.45 alleles per locus, of which 14 markers had high polymorphism (3 alleles/locus). Polymorphic Information Content (PIC) values obtained at 20 SSR loci ranged from 0.31 (Ce0078) to 0.85 (HK34), with an average of 0.65. The genetic similarity coefficient within the accessions ranged from 0.39 to 1.00. All 253 accessions were classified into 2 groups at a genetic similarity level of 0.60; one of the groups (group 2) was divided into 8 sub-groups at a genetic similarity level of 0.64. Some accessions (such as 28279 and SP-19-009; SP-19-061 and SP-19-023; 28278 and SP-19-006) with a high genetic similarity coefficient (1.00) showed a very close genetic relationship, while others (such as 10063 and 11544) with a low genetic similarity coefficient (0.39) showed a fairly distant genetic relationship. The study's results provide a foundation for preserving and breeding taro in Vietnam. Five taro accessions (28211, SP-19-017, T.3578, T.3515, and 10098) carrying specific alleles that could be identified by 6 SSR markers (uq55–112, uq73–164, HK35, Ce0078, HK22, and HK31) were detected. Furthermore, the SSR marker approach showed the potential application in identifying genetic relationships and distinguishing different taro cultivars. [ABSTRACT FROM AUTHOR]

Purpose: Sympathetic ophthalmia (SO) is considered as an autoimmune disease with unclear mechanisms. This study investigated the relationship between HLA polymorphisms and SO. Methods: HLA typing was performed using the LABType reverse SSO DNA typing method. The allele and haplotype frequencies were assessed using the PyPop software. Statistical significance of genotype distributions between 116 patients and 84 healthy individuals (control) was determined using Fisher's exact test or Pearson's chi-squared test. Results: The SO group had a higher frequency of HLA-DRB1 * 04:05, HLA-DQB1 * 04:01, DRB1 * 04:05-DQB1 * 04:01 haplotype as compared to the control group (Pc < 0.001 for all). Conclusion: This study revealed that DRB1 * 04:05 and DQB1 * 04:01 alleles, as well as DRB1 * 04:05-DQB1 * 04:01 haplotye could be potential risk factors for SO. [ABSTRACT FROM AUTHOR]

Recent studies have identified a correlation between chronic viral hepatitis and cognitive impairment, yet the underlying mechanisms remain unclear. This study investigated the influence of TGFB1 genetic polymorphisms on cognitive function in individuals with and without hepatitis infections, hypothesizing that these polymorphisms and the viral hepatitis‐induced inflammatory environment interact to affect cognitive abilities. Participants (173 with viral hepatitis and 258 healthy controls) were recruited. Genotyping of TGFB1 SNPs was performed using the C2‐58 Axiom Genome‐Wide TWB 2.0 Array Plate. Cognitive function was assessed using the MMSE and MoCA tests. Our results showed that healthy individuals carrying the C allele of rs2241715 displayed better performance in sentence writing (p = 0.020) and language tasks (p = 0.022). Notably, viral hepatitis was found to moderate the impact of the rs2241715 genotype on language function (p = 0.002). Similarly, those carrying the T allele of rs10417924 demonstrated superior orientation to time (p = 0.002), with viral hepatitis modifying the influence of the SNP on this particular cognitive function (p = 0.010). Our findings underscore the significant role of TGFβ1 in cognitive function and the moderating impact of viral hepatitis on TGFB1 SNP effects. These findings illuminate the potential of TGFB1 as a therapeutic target for cognitive impairment induced by viral hepatitis, thus broadening our understanding of TGFβ1 functionality in the pathogenesis of neurodegeneration. [ABSTRACT FROM AUTHOR]

Background/Aim: Matrix metalloproteinase-2 (MMP-2) has been implicated in the pathogenesis of breast cancer (BC). However, there is limited research on the role of MMP-2 genotypes in BC risk. This study aimed to investigate the associations between two MMP-2 promoter polymorphisms, rs243865 and rs2285053, and BC risk. Materials and Methods: MMP-2 genotypes were analyzed using PCR-based RFLP methodology in a cohort comprising 1,232 BC cases and 1,232 controls. Results: Genotypic frequencies of MMP-2 rs243865 and rs2285053 in controls were consistent with Hardy-Weinberg equilibrium (p=0.3702 and 0.2036, respectively). There were no significant differences in the distribution of rs243865 and rs2285053 genotypes between BC cases and controls (p for trend=0.1602 and 0.2170, respectively). Variant genotypes at rs243865 and rs2285053 appeared to confer a protective effect, although not statistically significant (all p>0.05). Similarly, the variant T allele at rs243865 and rs2285053 showed a non-significant trend towards decreased BC risk (OR=0.84 and 0.89, 95%CI=0.69-1.02 and 0.78-1.02, p=0.0811 and 0.1043, respectively). There was no interaction observed between MMP-2 rs243865 or rs2285053 genotypes and age. Stratified analysis did not reveal significant associations between MMP-2 rs243865 or rs2285053 genotypes and triple-negative breast cancer (TNBC) (p=0.6458 and 0.8745, respectively). Among both TNBC and non-TNBC cases, none of the variant genotypes at rs243865 or rs2285053 showed significant associations with TNBC (all p>0.05). Conclusion: MMP-2 rs243865 and rs2285053 genotypes appear to have a minimal impact on individual susceptibility to BC or TNBC. [ABSTRACT FROM AUTHOR]

Purpose: Dientamoeba fragilis (D. fragilis) is a common intestinal protozoan with a global distribution. In the present study, we aimed to determine genetic diversity of D. fragilis isolates with multilocus sequence typing (MLST) in the southwest of Turkey and analyse the clinical findings. Materials and Methods: The study included faecal samples from 200 individuals in Aydin, Turkey. The positivity of D. fragilis was determined with 18 S rRNA gene-based PCR assay. Six nested-PCR reactions were set to amplify partial D. fragilis housekeeping genes in the positive samples. The sequences were aligned with the references from GenBank to detect nucleotide polymorphisms and haplotypes. Additionally, the clinical findings and demographic characteristics of patients were statistically analysed between D. fragilis-infected and non-infected cases. Results: The positivity of D. fragilis was 16% (32 out of 200 cases) with 18 S rRNA based-PCR, and all were classified as "genotype 1". The analysis of six MLST loci revealed different haplotypes only at one locus; the remaining five loci exhibited no polymorphisms. The haplotypes in the present study were identical to at least one previously reported reference, except the locus "large subunit of RNA polymerase II" locus. There were no significant differences in any of the clinical findings or demographic characteristics between the infected and non-infected groups. Conclusions: Our study revealed a low genetic diversity of D. fragilis isolates from Turkey, like other countries including Italy, Denmark, the UK, Australia, and Brazil. The high degree of sequence similarity in housekeeping genes indicated the clonal distribution of D. fragilis. [ABSTRACT FROM AUTHOR]

Background: Aldosterone synthase (CYP11B2) is crucial for aldosterone production, and variations in its gene may influence type 2 diabetes mellitus (T2DM) development. This study explores the link between two single nucleotide polymorphisms (SNPs) in the CYP11B2 gene - −344T/C and K173R and T2DM in the Moroccan population. Methods: The research involved 86 individuals with T2DM and 75 control subjects. Genotyping for the −344T/C and K173R SNPs was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Result: Results indicated significant differences in the genotype and allelic distribution of the CYP11B2 K173R polymorphism between T2DM patients and control subjects, with P-values of 0.02 and 0.04, respectively. The −344T/C polymorphism showed no significant genomic level differences, but its allelic variations were statistically significant (P=0.01), indicating a notable association between the C allele and T2DM. Furthermore, the K173R polymorphism was found to significantly increase T2DM risk, with a 2.34-fold higher risk in individuals carrying the KR genotype. The study also examined the combined effect of these SNPs. The dominant model analysis (TT vs. TC+CC and KK vs. KR+RR) showed significant differences between T2DM patients and controls for both SNPs. Additionally, a haplotype-based analysis revealed that the C-R haplotype was associated with an increased risk of T2DM. Conclusion: Our study suggests a significant association between the CYP11B2-K173R polymorphism and T2DM in the Moroccan population. Conversely, while the CYP11B2 -344T/C polymorphism exhibits a significant difference in allelic distribution, no significant difference is observed at the genomic level. [ABSTRACT FROM AUTHOR]

The CUBN gene polymorphisms have been implicated in the pathogenesis of diabetes mellitus, encompassing both type 1 diabetes and type 2 diabetes. Nevertheless, the outcomes have been erratic. We conducted a comprehensive review to examine the connections. The literature was obtained from PubMed, ISI Web of Science, EmBase, and Scopus databases. The systematic review of the relationships between CUBN gene polymorphisms and diabetes risk identified 8 studies based on the search technique and inclusion criteria. Every single study that was considered used a casecontrol methodology. There was no study that was not considered to be of "high" or "medium" quality. The CUBN gene polymorphism in type 2 diabetes was the subject of five investigations involving 54,0970 patients and 435,312 controls. The CUBN gene polymorphism in type 1 diabetes was the subject of three studies including 19,660 patients and 388,374 controls. The majority of the research were conducted in European communities, with one study specifically focusing on American groups. Finally, the investigations varied in the platform utilized for genotyping or sequencing. While the study uncovers a new connection between the CUBN gene polymorphism and type 1 diabetes, the specific mechanism by which this polymorphism increases the chance of developing diabetes requires additional exploration. The results offer fresh perspectives on the genetic structure of albuminuria and emphasize specific genes and pathways that can be targeted to prevent kidney damage associated with type 2 diabetes. Our findings suggest that the CUBN gene may play a significant role in the genetic vulnerability to diabetes in individuals of European and American descent. Nevertheless, the generalizability of these findings to other ethnic groups remains unknown due to the previously documented significant variations in the genetic structure of CUBN gene between European and African populations. [ABSTRACT FROM AUTHOR]

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Genetic polymorphisms in drug metabolizing enzymes and drug–drug interactions are major sources of inadequate drug exposure and ensuing adverse effects or insufficient responses. The current challenge in assessing drug–drug gene interactions (DDGIs) for the development of precise dose adjustment recommendation systems is to take into account both simultaneously. Here, we analyze the static models of DDGI from in vivo data and focus on the concept of phenoconversion to model inhibition and genetic polymorphisms jointly. These models are applicable to datasets where pharmacokinetic information is missing and are being used in clinical support systems and consensus dose adjustment guidelines. We show that all such models can be handled by the same formal framework, and that models that differ at first sight are all versions of the same linear phenoconversion model. This model includes the linear pharmacogenetic and inhibition models as special cases. We highlight present challenges in this endeavor and the open issues for future research in developing DDGI models for recommendation systems. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusionsThis meta-analysis aims to evaluate the potential link between common variations in the Surfactant Protein-B (SFTPB) gene and the risk of bronchopulmonary dysplasia (BPD) in preterm neonates.All pertinent articles published prior to February 1, 2024, in PubMed, Web of Science, EMBASE, CNKI, and Scopus databases were reviewed.Nineteen case-control studies involving 1149 BPD cases and 1845 non-BPD controls, were analyzed. Combined data indicated a significant link between SFTPB −18 A > C and Intron 4 VNTR polymorphisms with increased BPD susceptibility, while the 1580 C > T polymorphism provides a protective impact on BPD initiation.Pooled data indicated a significant association between SFTPB −18 A > C and Intron 4 VNTR polymorphisms with increased BPD risk, whereas the 1580 C > T polymorphism confers protection. These findings suggest a genetic susceptibility to BPD, underscoring the complex interplay of different genetic elements in its development. [ABSTRACT FROM AUTHOR]

Abrocitinib is a selective Janus kinase 1 inhibitor approved for the treatment of atopic dermatitis. It is metabolized primarily by cytochrome P450 (CYP) 2C19 (approximately 53%) and CYP2C9 (approximately 30%), which form 2 active metabolites. The pharmacologic activity of abrocitinib is attributable to the unbound exposures of abrocitinib and those metabolites with active moiety area under the plasma concentration–time curve (AUC) considered the best measure of the total pharmacological effect. The effect of CYP2C19 and/or CYP2C9 genotypes on abrocitinib and active moiety exposures were evaluated using a meta‐analysis of the noncompartmental estimates of exposure pooled from 10 clinical studies. A linear mixed‐effects model was developed on the basis of the power model to evaluate the effect of CYP2C19 and/or CYP2C9 genotypes on exposure (i.e., abrocitinib AUC and peak plasma concentration, active moiety AUC and peak plasma concentration). The genotypes were evaluated individually and as a combined phenotype effect. When evaluating the poor metabolizers of CYP2C19 or CYP2C9 individually, the estimated increases were 44.9% and 42.0% in active moiety AUC, respectively. The combined phenotype models showed a 0.6% decrease, and 25.1% and 10.5% increases in the active moiety AUC for “elevated,” “mixed,” and “reduced” metabolizers, respectively. Overall, the active moiety exposures did not appear to be affected to a clinically meaningful extent by different genotypes of CYP2C19 and/or CYP2C9. [ABSTRACT FROM AUTHOR]