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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]

AbstractBackgroundMethodResultsConclusionThis study aimed to investigate the association of rs12976445 polymorphism in the promoter region of miR-125a and rs2114358 in the precursor region of miR-1206 to breast cancer susceptibility.A total of 230 participants (110 breast cancer and 120 controls) enrolled in this study and extracted genomic DNA. The genotypes were determined by the Tetra-ARMS method. The allele and genotype frequencies were determined.Allele variation in the rs12976445 (miR-125a) sequence increased the risk of breast cancer; a significant relationship was observed between breast cancer and allele change in individuals with the C allele (p = 0.01). However, allele variation in the rs2114358 (miR-1206) decreased the risk of breast cancer in individuals with allele A (p = 0.01). In silico study showed that allele change was associated with a reduction in structural stability.Therefore, the rs12976445 variant can be considered a risk factor for breast cancer, and the rs2114358 variant is a protective factor against it. [ABSTRACT FROM AUTHOR]

Introduction: In this retrospective study, it was aimed to evaluate effects of Toll Like Receptor 4 (TLR4) and Toll Like Receptor 2 (TLR 2) gene polymorphisms on clinical outcomes in acute non-biliary pancreatitis patients. Methods: A total of 108 acute non-biliary pancreatitis patients (ANBP) were retrospectively subjected to the study. Gender, age, number of attacks, hospitalization duration, amylase, lipase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), leukocyte, C-reactive protein (CRP), total bilirubin, direct bilirubin, Atlanta score, ultrasonography (USG), Computer Tomography (CT) and patient outcome differences between TLR 4 Rs4986790, TLR 4 Rs4986791 and TLR 2 groups were evaluated. Results: According to TLR 4 Rs4986790 groups, females were significantly common in AA sequence (AA) group with statistically significant difference (p<0.05). Leukocyte mean of AG sequence (AG) group was significantly higher than of AA group (p<0.05). All parameter differences between TLR 4 Rs4986791 and TLR 2 groups were statistically insignificant (p>0.05). there was a statistically significant correlation between TLR 4 Rs4986790 and gender (r=0.265; p<0.01), Leukocyte (r=0.200; p<0.05) and Pseudocyst (r=0.203; p<0.05). TLR 4 Rs4986790 gene polymorphism had significant effect on leukocyte level in acute non-biliary pancreatitis patients (OR: -0.1.900; p<0.05). Predictive value of leukocyte for TLR 4 Rs4986790 was statistically significant (Area Under Curve: 0.624; p<0.05). For 7.65 leukocyte cut off value, sensitivity for AA gene polymorphism was 84.2% and specificity was 40.5% Conclusion: Although the clinical and outcome parameters of ANBP patients in terms of TLR 4 Rs4986791 and TLR 2 do not show significant differences, research findings point to the diagnostic value of patients' leukocyte parameters in determining TLR-4 Rs4986790 ploimorphism groups. [ABSTRACT FROM AUTHOR]

Background: This study explores whether the impact of environmental factors (community services usage, CSU) on geriatric depression is mediated by psychological resilience and moderated by the COMT (catechol-O-methyltransferase) gene val158met polymorphism. Methods: The data consists of 13,512 entries from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) collected in the years 2008, 2011, 2014, and 2018. The study employed a Random Intercept Cross-Lagged Panel Model (RI-CLPM) to examine the relationship between CSU and geriatric depression, including the mediating effect of psychological resilience and the moderating role of the comt gene val158met gene polymorphism in this relationship. Results: Lower CSU at earlier assessments were significantly associated with more severe geriatric depression in subsequent evaluations.Psychological resilience was found to partially mediate the relationship between CSU and depression.Differential impacts were observed among various gene genotypes; specifically, the val genotype demonstrated a significantly greater influence of CSU on subsequent psychological resilience and on subsequent depression compared to the met genotype. Conclusion: Enhancement in CSU can predict subsequent geriatric depression. The relationship between the CSU and depression can be mediated by psychological resilience, with genetics modulating the pathway from CSU through psychological resilience to depression. Multidisciplinary interventions focused on enhancing community service quality, boosting psychological resilience, and mitigating depression are likely to benefit the older adults's emotional and psychological well-being. [ABSTRACT FROM AUTHOR]

Single-nucleotide polymorphisms (SNPs) represent the most prevalent form of genomic polymorphism and are extensively used in population genetics research. Using dd-RAD sequencing, a high-throughput sequencing method, we investigated the genome-level diversity, population structure, and phylogenetic relationships among three morphological forms of the widely distributed taxon Cryptotaenia japonica Hassk., which is native to East Asia. Our study aimed to assess the species status of C. japonica according to its genetic structure and genetic diversity patterns among 66 naturally distributed populations, comprising 26 C. japonica f. japonica, 36 C. japonica f. dissecta (Y. Yabe) Hara and 4 C. japonica f. pinnatisecta S. L. Liou accessions. Based on genomic SNP data generated by dd-RAD sequencing, we conducted genetic diversity, principal component, neighbor-joining (NJ) phylogenetic, admixture clustering, and population differentiation analyses. The findings revealed the following: (1) 5,39,946 unlinked, high-quality SNPs, with mean p, HO, HE and FIS values of 0.062, 0.066, 0.043 and -0.014, respectively, were generated; (2) population divergence was unaffected by isolation through distance; (3) six main distinct regions corresponding to geographic locations and exhibiting various levels of genetic diversity were identified; (4) pairwise FST analysis showed significant (P < 0.05) population differentiation in 0%-14% of populations among the six regions after sequential Bonferroni correction; and (5) three migration events (historical gene flow) indicated east? west directionality. Moreover, contemporary gene flow analysis using Jost's D, Nei's GST, and Nm values highlighted the middle latitude area of East Asia as a significant contributor to genetic structuring in C. japonica. Overall, our study elucidates the relatively low genetic differentiation and population structure of C. japonica across East Asia, further enhancing our understanding of plant lineage diversification in the Sino-Japanese Floristic Region. [ABSTRACT FROM AUTHOR]

Aim Method Results Conclusion To clarify the association between genetic factors related to angiogenesis and feeling of incomplete bladder emptying among older community‐dwelling individuals.A cross‐sectional study of 1762 (607 men and 1155 women) older Japanese individuals aged 60–79 years with data on rs3025020 was conducted, because vascular endothelial growth factor (VEGF), which contributes to the progression of angiogenesis, has been reported to be positively associated with the minor allele (T) of polymorphism rs3025020.In the study population, 155 (103 men and 52 women) had feeling of incomplete bladder emptying. With rs3025020 (C/C) as the reference group, rs3025020 (T/T) was associated with a significantly higher odds ratio (OR) for feeling of incomplete bladder emptying. The adjusted ORs and 95% confidence intervals were 3.01(1.53, 5.93) in men and 2.48 (1.09, 5.66) in women, respectively.VEGF polymorphism rs3025020 was associated with feeling of incomplete bladder emptying among older community‐dwelling individuals. Development of angiogenesis could be associated with feeling of incomplete bladder emptying in older individuals. Geriatr Gerontol Int 2024; ••: ••–••. [ABSTRACT FROM AUTHOR]

Background: Albeit smoking cessation has unequivocal health benefits, attempts to quit are not unanimous, even in patient populations at high risk for smoking-related diseases cessation. Allelic variations of enzymes involved in dopamine metabolism are being considered as candidates for nicotine addiction. We set out to assess whether rs4680 G/A and rs2235186 G/A polymorphisms of COMT and MAO-A, respectively are associated with the ability to quit smoking in chronic inflammatory pulmonary disease patients. Methods: Patients managed for chronic inflammatory pulmonary disease by the Department of Pulmonology (University of Debrecen, Hungary), with a current or past smoking habit were included in the current analysis. The study was designed in line with the STROBE statement for cross-sectional studies and was approved by the National Center for Public Health, Hungary. Genomic DNA was extracted from peripheral blood specimens. SNPs were genotyped using TaqMan SNP genotyping assays. Results: rs4680 COMT polymorphism showed significant effect for successful smoking cessation in patients with pulmonary disease. Accordingly, A/A subjects had lower odds for successful smoking cessation (odds ratio 0.37; 95% confidence interval 0.20–0.69, p = 0.002 (additive model). On the other hand, patients homozygous for the minor allele (A) at rs2235186 of MAO-A showed a non-significant trend toward increased odds for successful smoking cessation. Conclusions: The presence of the minor allele for rs4680 COMT was shown to decrease the odds for successful smoking cessation, a finding that may be interpreted in view of the altered balance between tonic and phasic dopamine release. [ABSTRACT FROM AUTHOR]

Introduction: Research data show the impact of the endocannabinoid system on psychosis through its neurotransmission homeostatic functions. However, the effect of the endocannabinoid system genetic variability on the relationship between cannabis use and psychosis has been unexplored, even less in first-episode patients. Here, through a case-only design, we investigated the effect of cannabis use and the genetic variability of endocannabinoid receptors on clinical and cognitive outcomes in first-episode psychosis (FEP) patients. Methods: The sample comprised 50 FEP patients of European ancestry (mean age (sd) = 26.14 (6.55) years, 76% males), classified as cannabis users (58%) or cannabis non-users. Two Single Nucleotide Polymorphisms (SNP) were genotyped at the cannabinoid receptor type 1 gene (CNR1 rs1049353) and cannabinoid receptor type 2 gene (CNR2 rs2501431). Clinical (PANSS, GAF) and neuropsychological (WAIS, WMS, BADS) assessments were conducted. By means of linear regression models, we tested the main effect of cannabis use and its interaction with the polymorphic variants on the clinical and cognitive outcomes. Results: First, as regards cannabis effects, our data showed a trend towards more severe positive symptoms (PANSS, p = 0.05) and better performance in manipulative abilities (matrix test-WAIS, p = 0.041) among cannabis users compared to non-users. Second, concerning the genotypic effects, the T allele carriers of the CNR1 rs1049353 presented higher PANSS disorganization scores than CC homozygotes (p = 0.014). Third, we detected that the observed association between cannabis and manipulative abilities is modified by the CNR2 polymorphism (p = 0.022): cannabis users carrying the G allele displayed better manipulative abilities than AA genotype carriers, while the cannabis non-users presented the opposite genotype-performance pattern. Such gene–environment interaction significantly improved the overall fit of the cannabis-only model (Δ-R² = 8.4%, p = 0.019). Discussion: Despite the preliminary nature of the sample, our findings point towards the role of genetic variants at CNR1 and CNR2 genes in the severity of the disorganized symptoms of first-episode psychosis and modulating cognitive performance conditional to cannabis use. This highlights the need for further characterization of the combined role of endocannabinoid system genetic variability and cannabis use in the understanding of the pathophysiology of psychosis. [ABSTRACT FROM AUTHOR]

Lactase persistence (LP) — the genetic trait that determines the continued expression of the enzyme lactase into adulthood — has undergone recent, rapid positive selection since the advent of animal domestication and dairying in some human populations. While underlying evolutionary explanations have been widely posited and studied, the molecular basis of LP remains less so. This review considers the genetic and epigenetic bases of LP. Multiple single‐nucleotide polymorphisms (SNPs) in an LCT enhancer in intron 13 of the neighbouring MCM6 gene are associated with LP. These SNPs alter binding of transcription factors (TFs) and likely prevent age‐related increases in methylation in the enhancer, maintaining LCT expression into adulthood to cause LP. However, the complex relationship between the genetics and epigenetics of LP is not fully characterised, and the mode of action of methylation quantitative trait loci (meQTLs) (SNPs affecting methylation) generally remains poorly understood. Here, we examine published LP data to propose a model describing how methylation in the LCT enhancer is prevented in LP adults. We argue that this occurs through altered binding of the TF Oct‐1 (encoded by the gene POU2F1) and neighbouring TFs GATA‐6 (GATA6), HNF‐3A (FOXA1) and c‐Ets1 (ETS1) acting in concert. We therefore suggest a plausible new model for LCT downregulation in the context of LP, with wider relevance for future work on the mechanisms of other meQTLs. [ABSTRACT FROM AUTHOR]

Background: Ischemic stroke (IS) is a major cause of death and disability worldwide. Genetic factors are important risk factors for the development of IS. The quinone oxidoreductase 1 gene (NQO1) has antioxidant, anti-inflammatory, and cytoprotective properties. Thus, in this study, we investigated the relationship between NQO1 gene polymorphism and the risk of IS. Methods: Peripheral blood was collected from 143 patients with IS and 124 the control groups in Yunnan, China, and NQO1 rs2917673, rs689455, and rs1800566 were genotyped. Logistic regression was used to analyze the relationship between the three NQO1 loci and IS susceptibility. The difference in the expression levels of NQO1 between the control groups and IS groups was verified using public databases and enzyme-linked immunosorbent assay. Results: The rs2917673 locus increased the risk of IS by 2.375 times in TT genotype carriers under the co-dominance model compared with CC carriers and was statistically associated with the risk of IS (OR = 2.375, 95% CI = 1.017–5.546, P = 0.046). In the recessive model, TT genotype carriers increased IS risk by 2.407 times compared with CC/CT carriers and were statistically associated with the risk of IS (OR = 2.407, 95% CI = 1.073–5.396, P = 0.033). Conclusions: NQO1 rs2917673 polymorphism is significantly associated with IS. Mutant TT carriers are risk factors for IS. [ABSTRACT FROM AUTHOR]

Background: Lipocalin-2 (LCN2), a neutrophil gelatinase-associated protein, plays an important role in iron homeostasis, infection, and inflammation. Polymorphism in the LCN2 gene is linked to various diseases such as cardiovascular disease, renal damage, and colorectal and pancreatic cancer. Identifying deleterious functional non-synonymous SNPs in the LCN2 gene is crucial in understanding how these genetic variations affect its structure and function. Methods: Several in silico tools such as SIFT, Polyphen-2, PROVEAN, PREDICT SNP, MAPP, and SNAP2 followed by I-MUTANT 2.0, MUpro, ConSurf, and NetsurfP-2.0, secondary structure of the protein by SOPMA and PSIPRED, while its interaction with other genes and proteins was analyzed using GeneMANIA and STRING, respectively, and AlphaFold for protein's 3D structure prediction. Results: The study identified 6 potentially harmful nsSNPs (rs11556770, rs139418967, rs142623708, rs200107414, rs201365744, rs368926734) and their structure and function were analyzed using prediction tools. I-MUTANT 2.0 predicted an increase in stability with the nsSNPs rs139418967, while the other shows decrease in protein stability with the 6 nsSNPs (rs11556770, rs139418967, rs142623708, rs200107414, rs201365744, rs368926734) which was validated using MUpro. ConSurf identified the 6 high-risk nsSNPs to be in the conserved regions of the protein. The result showed that rs11556770, rs139418967, rs142623708, rs200107414, rs201365744, and rs368926734 were found to be highly conserved and the variant amino acids. According to NetsurfP-2.0 server, the result showed that rs11556770 (Q39H), rs139418967 (L6P), rs368926734 (Y135H) were predicted to be exposed and rs142623708 (M71I), rs200107414 (Y52C), rs368926734 (Y135) were buried. The PSIPRED server analysis indicated that the predominant secondary structure was a strand, with lesser occurrences of coil and helix. Conclusion: Overall, the study identified detrimental nsSNPs of LCN2 using computational analysis which could be used for large population-based investigations and diagnosis. [ABSTRACT FROM AUTHOR]

Background: Postoperative nausea and vomiting are common complications after surgery, and female patients are more likely to experience these adverse events. The goal of this study was to explore the relationship between the CHRM3 rs2165870 polymorphism and postoperative vomiting incidence in female patients who underwent laparoscopic surgery. Methods: Two hundred female patients who underwent elective laparoscopic surgery with subsequent patient-controlled intravenous analgesia using dexmedetomidine and sufentanil were prospectively enrolled. The CHRM3 rs2165870 and KCNB2 rs349358 polymorphisms were genotyped using MassARRAY SNP typing technology. Demographic data and preoperative laboratory results of all patients were recorded. Postoperative analgesia-related information, incidence of postoperative nausea and vomiting, and other adverse events were followed up and recorded for analysis. Results: No significant differences were observed in any of the demographic characteristics of these patients among the different genotype carriers (P>0.05). The percentages of patients with each genotype of CHRM3 were 67% (GG), 28.5% (GA) and 4.5% (AA). We found that the AA or A allele of the CHRM3 rs2165870 polymorphism elevated the risk of postoperative vomiting (AA versus GG; OR, 6.94; 95% CI, 1.49–32.46; P = 0.014; A versus G; OR, 2.52; 95% CI, 1.22–5.19; P = 0.012). The percentages of patients with each genotype of KCNB2 were 84.5% (TT), 15.5% (CT) and 0% (CC). There were no significant differences in the postoperative nausea or vomiting rate across the KCNB2 rs349358 polymorphisms (P>0.05). Conclusion: The CHRM3 rs2165870 polymorphism is associated with the occurrence of postoperative vomiting in female patients who have undergone laparoscopic surgery. The AA genotype or A allele of the CHRM3 rs2165870 polymorphism elevates the risk of postoperative vomiting. Trial registration: www.chictr.org.cn, registration number: ChiCTR2200062425. [ABSTRACT FROM AUTHOR]

Avascular necrosis (AVN) is a debilitating condition characterized by bone tissue death due to inadequate blood supply, leading to joint dysfunction and collapse. This study investigates the potential association between AVN and COVID-19, focusing on genetic factors such as NOS3 polymorphisms. A total of 180 individuals were included, comprising 120 COVID-19 patients and 60 healthy controls. Clinical, haematological, biochemical, and genetic parameters were assessed. Results revealed significant differences in respiratory and heart rates, haematological counts, and biochemical markers between AVN and control groups. Genetic analysis showed a higher prevalence of the TG genotype and G allele in NOS3 rs1799983 polymorphism among AVN patients. Additionally, NOS3 rs2070744 polymorphism correlated with various clinical parameters, including blood pressure, heart rate, and haematological indices. This study highlights the potential role of genetic factors in predisposing individuals to AVN following COVID-19 infection. [ABSTRACT FROM AUTHOR]

Introduction: Alveolar echinococcosis (AE) is a life-threatening disease in humans caused by the larval stage of Echinococcus multilocularis. Domestic animals, dogs, foxes, and small mammals constitute the circular chain of AE. To evaluate the infection, distribution, and genetic polymorphism of AE in the Ili Prefecture (Nilka, Xinyuan and Zhaosu), we conducted this survey. Methods: In June and July 2018, 267 small mammals were captured using waterinfusion and mousetrap methods. Combined pathogenic and molecular biological methods were used to observe the histopathology of Echinococcus carried by rodents, amplify the mitochondrial nad1 gene of the pathogen, and investigate the genotype and haplotype diversity of Echinococcus in rodents in Ili Prefecture. Results: Morphological identification revealed that these captured small mammals belonged to three species, with Microtus gregalis being the dominant species (183/267). Pathological and molecular biological results confirmed that E. multilocularis was the pathogen of echinococcosis in small mammals, with an infection rate of 15.73% (42/267). Among the three areas sampled, the highest infection rate of rodents was 25.45% (14/55) in Nilka County. However, there was no significant difference in the infection rates between regions (χ² = 5.119, p > 0.05). Of the three captured rodent species, M. gregalis had the highest infection rate of 17.49% (32/183), but there was no significant difference in infection rates between the rodent species (χ² = 1.364, p > 0.05). Phylogenetic analyses showed that the nad1 gene sequences obtained in this study clustered in the same clade as isolates from China. These isolates contained 21 haplotypes (Hap_1-21); Hap_2 was the most common haplotype (9/42). Furthermore, haplotype diversity (0.925 ± 0.027) and nucleotide diversity (0.01139 ± 0.00119) were higher in the Ili Prefecture than in other regions, indicating that population differentiation was high. Tajima's D and Fu's Fs tests were negative (p > 0.10), indicating that the population had expanded. The low fixation index (Fst) ranged from 0.00000 to 0.16945, indicating that the degree of genetic differentiation was different among different populations. Discussion: In summary, Ili Prefecture is a high incidence area of AE, and Microtus spp. may play an important role in the transmission of AE in this area. The results of this study provide basic data for further study of the molecular epidemiology, genetic differences, and control of E. multilocularis in the Ili Prefecture, Xinjiang. [ABSTRACT FROM AUTHOR]

Background: The success of competitive alpine skiers with respective to their world ranking (WR) positions might be associated with prominent gene polymorphisms. Methods: Twenty-six competitive alpine skiers were followed from 2015 to 2019 for their WR positions (FIS-ranking). Using PCR, the genotypes of ACE-I/D, TNC, ACTN3, and PTK2 were identified. The correlations between the discipline-specific WR position (slalom—SL, giant slalom—GS, super G—SG, downhill—DH, and alpine combined—AC) and gene polymorphisms were analyzed concerning an influence with multivariate regression models. Results: The WR position and the ACE gene as well as the copy number of the ACE I-allele exhibited reciprocal relationships for speed specialists (SG and DH) but not for technical specialists (SL and GS). Similarly, the gene polymorphisms ACTN3 and (partly) PTK2 were associated with the WR position in disciplines characterized by a high number of turns (technical specialists—SL and GS) and speed (speed-specialists—SG and DH), respectively. Conclusions: Our findings emphasize the contributions of aerobic and cardiovascular metabolism in fueling muscle work and recovering from muscle fatigue for competitive success in slalom-driven skiing disciplines and highlight the contributions of sequence variants in the genes ACE, TNC, and ACTN3. [ABSTRACT FROM AUTHOR]

Background: Obsessive–compulsive disorder (OCD) is a debilitating disorder that has multifactorial etiology including genetic, neurobiological, cognitive, and environmental influences. Genetic studies have focused on the genes of the serotonin system. This study aimed to look for the possible relation between the polymorphism in the promotor region of the serotonin transporter gene and obsessive–compulsive disorder in the Egyptian population. Results: This study included 94 OCD patients and 116 healthy control individuals. Blood samples were collected from all participants for DNA extraction and genotyping. The assessment of patients was done by application of the structured clinical interview according to DSM-V, the dimensional Yale-Brown Obsessive–Compulsive Scale. There was an association between serotonin transporter gene polymorphism and OCD development. The carriage of the short allele was a risk factor for having OCD. Conclusion: Obsessive–compulsive disorder is associated with serotonin transporter gene polymorphism. This will contribute to considering the genetic information of patients for the prediction of best drug response and tolerability by personalizing the choice of treatment. [ABSTRACT FROM AUTHOR]

Purpose: Alzheimer's disease (AD) is a common neurodegenerative disease, which can lead to cognitive impairment and dementia. Since AD is tightly associated with aging and cellular senescence, objective of this study was to investigate the association between senescence-related genes and proteins (SRGs and SRPs) and the development of AD. Design: The whole study was based on transcriptomic analysis of control and AD brain tissues and Mendelian randomization (MR) analysis. Methods: For transcriptomic analysis, GSE5281 dataset from GEO database contains the transcriptomic data of human brain tissues (n = 161) from control group and AD patients. The expression of SRGs in control and AD brain tissues were compared by Student's t test. For MR analysis, the instrumental singlenucleotide polymorphisms (SNPs) associated with 110 SRPs were filtered and selected from a large genome-wide association study (GWAS) for plasma proteome. The causality between plasma levels of SRPs and AD was explored using GWAS data of AD from Lambert et al. (17,008 cases and 37,154 controls) and further validated by using data from FinnGen consortium (6,489 patients and 170,489 controls). MR estimate was performed using the inversevariance weighted (IVW) method and the heterogeneity and pleiotropy of results were tested. Results: Transcriptomic analysis identified 36 up-regulated (including PLAUR) and 8 down-regulated SRGs in AD brain tissues. In addition, the MR results at both discovery and validation stages supported the causality between plasma levels of PLAUR (IVW-p = 3.04E-2, odds ratio [OR]= 1.15), CD55 (IVW-p = 1.56E-3, OR= 0.86), and SERPINE2 (IVW-p = 2.74E-2, OR= 0.91) and the risk of AD. Conclusion: Our findings identified that PLAUR, as an SRG, may take part in the development of AD and found that high plasma levels of PLAUR was associated with increased risk of AD, indicating that this gene was a risk factor for this disease and providing the rationale of existing drugs or new preventative and therapeutic strategies. [ABSTRACT FROM AUTHOR]

The most prevalent hip disease in neonates is developmental dysplasia of the hip (DDH). A timely and accurate diagnosis is required to provide the most effective treatment for pediatric patients with DDH. Heredity and gene variation have been the subject of increased attention and research worldwide as one of the factors contributing to the pathogenesis of DDH. Genome-wide association studies (GWAS), genome-wide linkage analyses (GWLA), and exome sequencing (ES) have identified variants in numerous genes and single-nucleotide polymorphisms (SNPs) as being associated with susceptibility to DDH in sporadic and DDH family patients. Furthermore, the DDH phenotype can be observed in animal models that exhibit susceptibility genes or loci, including variants in CX3CR1, KANSL1, and GDF5. The dentification of noncoding RNAs and de novo gene variants in patients with DDH-related syndrome has enhanced our understanding of the genes implicated in DDH. This article reviews the most recent molecular mechanisms and genetic factors that contribute to DDH. [ABSTRACT FROM AUTHOR]

Background: Sacituzumab govitecan (sacituzumab) emerged as an important agent in metastatic and locally recurrent HER2‐negative breast cancer treatment. UGT1A1 polymorphisms have also been shown to predict sacituzumab toxicity. Methods: In this retrospective study, we sought to evaluate the associations between UGT1A1 status, toxicity, and therapeutic outcomes in sacituzumab recipients with advanced breast cancer who underwent genotype testing for UGT1A1 alleles (N = 68). Results: We found 17 (25%) of our patients to be homozygous for UGT1A1*28 and 24 (35.3%) were heterozygous. Of seven African American patients with triple‐negative breast cancer, five were homozygous for UGT1A1*28 and two were heterozygous. Patients with a homozygous UGT1A1*28 genotype were significantly more likely to have treatment terminated because of adverse effects. However, the polymorphism was not associated with treatment discontinuation because of disease progression. Conclusion: This retrospective, real‐world analysis suggests potential clinical utility in UGT1A1 testing for patients receiving sacituzumab, but future trials are needed to confirm the association between genotypes and treatment outcomes. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions To explore the correlation between Fat mass and objectivity associated gene (FTO) rs9939609 polymorphism and susceptibility to polycystic ovary syndrome.Case–control studies on the relationship between FTO rs9939609 A/T polymorphism and PCOS were searched in PubMed, EMBASE, and Web of Science according to inclusion and exclusion criteria. STATA 12.0 software was conducted for Meta‐analysis.Nine case–control studies were included, including 1410 cases in PCOS group and 1223 cases in healthy control group. The results of meta‐analysis showed that FTO rs9939609 gene polymorphism was associated with PCOS susceptibility, and the risk of developing PCOS was 1.19 times higher for T alleles carriers than for A alleles carriers, and some similar associations were observed in Asian populations.In summary, FTO rs9939609 gene polymorphism is significantly associated with PCOS susceptibility, especially in Asian populations. [ABSTRACT FROM AUTHOR]

Summary: Acyl‐CoA‐Binding Proteins (ACBPs) bind acyl‐CoA esters and function in lipid metabolism. Although acbp3‐1, the ACBP3 mutant in Arabidopsis thaliana ecotype Col‐0, displays normal floral development, the acbp3‐2 mutant from ecotype Ler‐0 characterized herein exhibits defective adaxial anther lobes and improper sporocyte formation.To understand these differences and identify the role of ERECTA in ACBP3 function, the acbp3 mutants and acbp3‐erecta (er) lines were analyzed by microscopy for anther morphology and high‐performance liquid chromatography for lipid composition.Defects in Landsberg anther development were related to the ERECTA‐mediated pathway because the progenies of acbp3‐2 × La‐0 and acbp3‐1 × er‐1 in Col‐0 showed normal anthers, contrasting to that of acbp3‐2 in Ler‐0. Polymorphism in the regulatory region of ACBP3 enabled its function in anther development in Ler‐0 but not Col‐0 which harbored an AT‐repeat insertion. ACBP3 expression and anther development in acbp3‐2 were restored using ACBP3pro (Ler)::ACBP3 not ACBP3pro (Col)::ACBP3. SPOROCYTELESS (SPL), a sporocyte formation regulator activated ACBP3 transcription in Ler‐0 but not Col‐0.For anther development, the ERECTA‐related role of ACBP3 is required in Ler‐0, but not Col‐0. The disrupted promoter regulatory region for SPL binding in Col‐0 eliminates the role of ACBP3 in anther development. [ABSTRACT FROM AUTHOR]

AbstractObesity is a common public health problem associated with serious, life-threatening complications. MicroRNAs (miRs) have modulating roles in the immune and inflammatory systems. Therefore, this study aimed to analyze the relationship between miR-146a and morbid obesity (MO) in a Turkish population. In this study, a total of 258 subjects (110 patients with MO and 148 controls) were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to analyze miR-146a rs2910164. Then, we examined the patients as males and females separately. The results of the analyses were evaluated for statistical significance. There was a significant difference in genotype and allele frequencies of miR-146a rs2910164 between patients with MO and control individuals. miR-146a rs2910164 CC genotype and C allele were shown to increase in the MO patients’ group compared to the control group (p = 0.000, p = 0.000, respectively). Also, the C allele was higher in both female and male patients compared to controls (p = 0.000, p = 0.000, respectively). High differences were also observed when the patients and the controls were compared according to CC versus GG + GC and GG versus GC + CC (p = 0.000, p = 0.000, respectively). A significant difference was found between the female/male patients and the female/male controls in terms of GG + GC versus CC (p = 0.000, p = 0.000, respectively). To the best of our knowledge, this is the first study to investigate the relationship between this variant and MO in Turkey. Our results showed that miR-146a rs2910164 is a valuable biomarker that can be used to distinguish between patients with MO and the healthy population. The findings can be extended by increasing the sample sizes with diverse ethnicities. [ABSTRACT FROM AUTHOR]

AbstractSeveral studies have reported the relationship between LIN28A gene polymorphisms (rs3811463 T > C and rs34787247 G > A) and cancer susceptibility, but the results are inconsistent and need further clarification. The current study aimed to evaluate their relationship and also to explore the relationship between LIN28A gene expression and immune infiltration, tumor stage, survival prognosis, and drug sensitivity in pan-cancer. The meta-analysis and data mining were completed by STATA software and the GSCA platform, respectively. The meta-analysis showed that the rs3811463 polymorphism was not associated with cancer susceptibility, while the rs34787247 polymorphism was associated with cancer susceptibility in the Chinese population [AA vs. GG: Odd Ratio (OR)=1.98, 95% Confidence Interval (CI)=1.35–2.89, PZ<0.001; GA vs. GG: OR = 1.17, 95%CI= 1.01–1.36, PZ=0.04; (AA + GA) vs. GG: OR = 1.24, 95%CI = 1.07–1.43, PZ=0.004; AA vs. (GA + GG): OR = 1.90, 95%CI = 1.30- 2.78, PZ=0.001; A vs. G: OR = 1.27, 95%CI = 1.12–1.44, PZ<0.001]. LIN28A gene expression was associated not only with immune infiltration, pathological stage, and survival prognosis of certain cancers, but also with sensitivity to multiple anticancer drugs, such as cisplatin, pazopanib, olaparib, and selumetinib. In conclusion, the current study suggested that the rs34787247 G > A polymorphism might be used as a cancer risk marker in the Chinese population, and LIN28A might serve as a prognostic marker and therapeutic target for certain cancers. [ABSTRACT FROM AUTHOR]

The ecological role of heritable phenotypic variation in free‐living populations remains largely unknown. Knowledge of the genetic basis of functional ecological processes can link genomic and phenotypic diversity, providing insight into polymorphism evolution and how populations respond to environmental changes. By quantifying the marine diet of Atlantic salmon, we assessed how foraging behaviour changes along the ontogeny, and in relation to genetic variation in two loci with major effects on age at maturity (six6 and vgll3). We used a two‐component, zero‐inflated negative binomial model to simultaneously quantify foraging frequency and foraging outcome, separately for fish and crustaceans diets. We found that older salmon forage for both prey types more actively (as evidenced by increased foraging frequency), but with a decreased efficiency (as evidenced by fewer prey in the diet), suggesting an age‐dependent shift in foraging dynamics. The vgll3 locus was linked to age‐dependent changes in foraging behaviour: Younger salmon with vgll3LL (the genotype associated with late maturation) tended to forage crustaceans more often than those with vgll3EE (the genotype associated with early maturation), whereas the pattern was reversed in older salmon. Vgll3LL genotype was also linked to a marginal increase in fish acquisition, especially in younger salmon, while six6 was not a factor explaining the diet variation. Our results suggest a functional role for marine feeding behaviour linking genomic diversity at vgll3 with age at maturity among salmon, with potential age‐dependent trade‐offs maintaining the genetic variation. A shared genetic basis between dietary ecology and age at maturity likely subjects Atlantic salmon populations to evolution induced by bottom‐up changes in marine productivity. [ABSTRACT FROM AUTHOR]

Learning is a taxonomically widespread process by which animals change their behavioural responses to stimuli as a result of experience. In this way, it plays a crucial role in the development of individual behaviour and underpins substantial phenotypic variation within populations. Nevertheless, the impact of learning in social contexts on evolutionary change is not well understood. Here, we develop game theoretical models of competition for resources in small groups (e.g. producer–scrounger and hawk–dove games) in which actions are controlled by reinforcement learning and show that biases in the subjective valuation of different actions readily evolve. Moreover, in many cases, the convergence stable levels of bias exist at fitness minima and therefore lead to disruptive selection on learning rules and, potentially, to the evolution of genetic polymorphisms. Thus, we show how reinforcement learning in social contexts can be a driver of evolutionary diversification. In addition, we consider the evolution of ability in our games, showing that learning can also drive disruptive selection on the ability to perform a task. [ABSTRACT FROM AUTHOR]

Simple Summary: Microsatellite instability (MSI) is crucial in colorectal cancer (CRC) due to deficient mismatch repair (MMR), often caused by MLH1 and MSH2 loss of function. This defect affects microsatellite loci globally. Recently, MSI at tetranucleotide loci has been identified as a distinct entity, potentially arising from isolated MSH3 loss of function due to its translocation to the cytoplasm under interleukin-6 (IL-6) influence. This study examined the impact of MSH3 and IL-6 signaling pathway polymorphisms (MSH3 exon 1, MSH3+3133A/G, IL-6-174G/C, IL-6R+48892A/C, and gp130+148G/C) on MSI types in sporadic CRC. A significant difference in gp130+148G/C genotypes (p = 0.037) and alleles (p = 0.031) was found, with the C allele being less common in tumors with di- and tetranucleotide instability (related to isolated MSH3 loss of function) compared to tumors without microsatellite instability. A functional polymorphism in gp130 may influence the IL-6 pathway, leading to MSI linked to MSH3 loss of function. Microsatellite instability (MSI) has been recognized as an important factor in colorectal cancer (CRC). It arises due to deficient mismatch repair (MMR), mostly attributed to MLH1 and MSH2 loss of function leading to a global MMR defect affecting mononucleotide and longer microsatellite loci. Recently, microsatellite instability at tetranucleotide loci, independent of the global MMR defect context, has been suggested to represent a distinct entity with possibly different consequences for tumorigenesis. It arises as a result of an isolated MSH3 loss of function due to its translocation from the nucleus to the cytoplasm under the influence of interleukin-6 (IL-6). In this study the influence of MSH3 and IL-6 signaling pathway polymorphisms (MSH3 exon 1, MSH3+3133A/G, IL-6-174G/C, IL-6R+48892A/C, and gp130+148G/C) on the occurrence of different types of microsatellite instability in sporadic CRC was examined by PCR–RFLP and real-time PCR SNP analyses. A significant difference in distribution of gp130+148G/C genotypes (p = 0.037) and alleles (p = 0.031) was observed in CRC patients with the C allele being less common in tumors with di- and tetranucleotide instability (isolated MSH3 loss of function) compared to tumors without microsatellite instability. A functional polymorphism in gp130 might modulate the IL-6 signaling pathway, directing it toward the occurrence of microsatellite instability corresponding to the IL-6-mediated MSH3 loss of function. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency and type 2 diabetes mellitus are risk factors for colorectal cancer, suggesting a role for vitamin D receptor (VDR) and insulin receptor (INSR) gene polymorphisms. We investigated the prevalence of the VDR-BsmI (rs1544410) and NsiI A/G-INSR (rs2059806) polymorphisms and their associations with colorectal adenoma (CRA) in a Romanian population. A case–control study was conducted with 110 participants (67 with CRA and 43 controls) who underwent colonoscopy. Polymerase chain reaction–restriction fragment length polymorphism analysis was used to determine the genotype and allele frequencies of the two polymorphisms. Regarding rs1544410 and CRA patients, genotype distribution was 35% B/B, 47% B/b, and 19% b/b. In the controls, the distribution was 21% B/B, 45% B/b, and 34% b/b. For rs2059806, 12% of CRA patients had A/A, 30% A/G, and 58% G/G, while 8% of the controls had A/A, 40% A/G, and 52% G/G. The recessive model showed an odds ratio of 2.84 (95% CI: 1.04–7.72, p = 0.033) for the b/b genotype. CRA patients with b/b or G/G genotypes were diagnosed at a younger age. The b allele of the rs1544410 was a risk factor for CRA. Patients with the b/b and G/G genotypes were diagnosed earlier. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a common neurodegenerative disease characterized by motor and non-motor symptoms including cognitive impairment and dementia. The etiopathogenesis of PD, as well as its protective and susceptibility factors, are still elusive. 3-Hydroxy-3-methyglutaryl coenzyme A reductase (HMGCR) is an enzyme regulating cholesterol synthesis. Single-nucleotide polymorphisms (SNPs) in the gene coding HMGCR have recently been correlated with the risk of Alzheimer's disease. Alternative splicing of exon 13 of the HMGCR transcript and its strongly associated HMGCR haplotype 7 (H7: rs17244841, rs3846662, rs17238540) may downregulate protein activity and cholesterol synthesis, with lower low-density lipoprotein cholesterol (LDL) levels associated with PD that may affect cognitive abilities. We genotyped three SNPs in the H7 HMGCR gene in 306 PD patients divided into three groups—without cognitive decline, with mild cognitive impairment (MCI), and with PD dementia—and in 242 healthy participants. A correlation between the rs17238540 genotype and PD susceptibility as well as a minor association between rs3846662 and cognitive status in PD patients was observed; however, the two-sided analysis of these groups did not reveal any significance. We observed a statistically significant elevated high-density lipoprotein cholesterol (HDL) plasma level in the minor allele carriers of rs17238540 and rs17244841 among PD patients. This study should be replicated in a larger population. [ABSTRACT FROM AUTHOR]

Tramdol is one of most popular opioids used for postoperative analgesia worldwide. Among Arabic countries, there are reports that its dosage is not appropriate due to cultural background. To provide theoretical background of the proper usage of tramadol, this study analyzed the association between several genetic polymorphisms (CYP2D6/OPRM1) and the effect of tramadol. A total of 39 patients who took tramadol for postoperative analgesia were recruited, samples were obtained, and their DNA was extracted for polymerase chain reaction products analysis followed by allelic variations of CYP2D6 and OPRM A118G determination. Numerical pain scales were measured before and 1 h after taking tramadol. The effect of tramadol was defined by the difference between these scales. We concluded that CYP2D6 and OPRM1 A118G single nucleotide polymorphisms may serve as crucial determinants in predicting tramadol efficacy and susceptibility to post-surgical pain. Further validation of personalized prescription practices based on these genetic polymorphisms could provide valuable insights for the development of clinical guidelines tailored to post-surgical tramadol use in the Arabic population. [ABSTRACT FROM AUTHOR]

Cancer is the leading cause of disease-related death among children. Vincristine (VCR), a key component of childhood cancer treatment protocols, is associated with the risk of peripheral neuropathy (PN), a condition that may be reversible upon drug discontinuation but can also leave lasting sequelae. Single nucleotide polymorphism (SNP) in genes involved in VCR pharmacokinetics and pharmacodynamics have been investigated in relation to an increased risk of PN. However, the results of these studies have been inconsistent. A retrospective cohort study was conducted to investigate the potential association of drug transporter genes from the ATP-binding cassette (ABC) family and the centrosomal protein 72 (CEP72) gene with the development of PN in 88 Caucasian children diagnosed with cancer and treated with VCR. Genotyping was performed using real-time PCR techniques for the following SNPs: ABCB1 rs1128503, ABCC1 rs246240, ABCC2 rs717620, and CEP72 rs924607. The results indicated that age at diagnosis (OR = 1.33; 95% CI = 1.07–1.75) and the ABCC1 rs246240 G allele (OR = 12.48; 95% CI = 2.26–100.42) were associated with vincristine-induced peripheral neuropathy (VIPN). No association was found between this toxicity and CEP72 rs924607. Our study provides insights that may contribute to optimizing childhood cancer therapy in the future by predicting the risk of VIPN [ABSTRACT FROM AUTHOR]

This case-control study investigated single nucleotide polymorphism (SNP) genotypes (CXC motif chemokine ligand 8 (CXCL8): rs2227306 and rs2227307 and tumor necrosis factor (TNF): rs1800629) in 85 patients with pain-related temporomandibular disorders (TMDp) and 85 controls to explore their associations with TMDp presence, pain intensity (low/high), and the presence of chronic arthralgia/myalgia. TMDp was diagnosed using a validated protocol, and polymorphisms were genotyped from buccal mucosa swabs using TaqMan assays. High pain intensity individuals had an increased risk for carrying minor allele "G" (rs2227307) and "T" (rs2227306) compared to controls (76% vs. 55.3%, p = 0.012; 72% vs. 54.1%, p = 0.030, respectively). Carriers of the minor allele "G" (rs2227307) were more prevalent in TMDp patients with arthralgia compared to controls (70.30% vs. 55.30%, p = 0.037). According to logistic regression, the most important predictors for high pain intensity were minor allele "G" of rs2227307 (OR 2.435, 95% CI 1.123–5.282), increasing age (OR 1.038, 95% CI 1.002–1.075), and female sex (OR 4.592, 95% CI 1.289–16.361). The explored gene polymorphisms were not significant risk factors for TMDp presence. These findings highlight the importance of genetic variations, particularly rs2227307, in understanding the diverse clinical manifestations of temporomandibular disorders. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has raised awareness of the virus's long-term non-pulmonary consequences. This study examined the relationship between genetic polymorphisms of VEGF and cardiac dysfunction and subclinical atherosclerosis in patients recovering from COVID-19. This study included 67 patients previously diagnosed with COVID-19. VEGF-936C/T, VEGF-634G/C, and VEGF-2578C/A statuses were determined. Conventional echocardiography and arterial parameters assessments were performed at inclusion and at six months after the first assessment. For VEGF-936C/T, dominant and over-dominant models showed a significant increase in ejection fraction at six months after COVID (p = 0.044 and 0.048) and was also a predictive independent factor for the augmentation index (β = 3.07; p = 0.024). The dominant model showed a rise in RV-RA gradient (3.702 mmHg) (p = 0.028 95% CI: 0.040–7.363), with the over-dominant model indicating a greater difference (4.254 mmHg) (p = 0.025 95% CI: 0.624–7.884). The findings for VEGF-634G/C were not statistically significant, except for a difference in TAPSE during initial evaluation, using the codominant model. For VEGF-2578C/A, a difference in ventricular filling pressure (E/E'ratio) was best described under the recessive model. Our research suggests that the VEG-936C/T genotype may impact the baseline level and subsequent changes in cardiac function and subclinical atherosclerosis. These findings offer valuable insights into the complex correlation between genetic polymorphisms and cardiovascular disfunction in long COVID patients. [ABSTRACT FROM AUTHOR]

Polymorphisms in the cholesteryl ester transfer protein (CETP) gene are known to be strongly associated with increased cardiovascular risk, primarily through their effects on the lipid profile and consequently on atherosclerotic risk. The acute heart rate response (AHRR) to physical activity is closely related to individual cardiovascular health. This study aimed to investigate the effect of CETP gene polymorphisms on AHRR. Our analysis examines the association of five single nucleotide polymorphisms (SNPs; rs1532624, rs5882, rs708272, rs7499892, and rs9989419) and their haplotypes (H) in the CETP gene with AHRR in 607 people from the Hungarian population. Individual AHRR in the present study was assessed using the YMCA 3-min step test and was estimated as the difference between resting and post-exercise heart rate, i.e., delta heart rate (ΔHR). To exclude the direct confounding effect of the CETP gene on the lipid profile, adjustments for TG and HDL-C levels, next to conventional risk factors, were applied in the statistical analyses. Among the examined five SNPs, two showed a significant association with lower ΔHR (rs1532624—Cdominant: B = −8.41, p < 0.001; rs708272—Gdominant: B = −8.33, p < 0.001) and reduced the risk of adverse AHRR (rs1532624—Cdominant: OR = 0.44, p = 0.004; rs708272—Gdominant: OR = 0.43, p = 0.003). Among the ten haplotypes, two showed significant association with lower ΔHR (H3—CAGCA: B = −6.81, p = 0.003; H9—CGGCG: B = −14.64, p = 0.015) and lower risk of adverse AHRR (H3—CAGCA: OR = 0.58, p = 0.040; H9—CGGCG: OR = 0.05, p = 0.009) compared to the reference haplotype (H1—AGACG). Our study is the first to report a significant association between CETP gene polymorphisms and AHRR. It also confirms that the association of the CETP gene with cardiovascular risk is mediated by changes in heart rate in response to physical activity, in addition to its effect on lipid profile. [ABSTRACT FROM AUTHOR]

Background: Sporotrichosis is a chronic granulomatous infection of the skin and subcutaneous tissue that can affect any organ through lymphatic spread. The prevalence of sporotrichosis infections is increasing and its treatment is challenging as there are no unified and standard diagnostic techniques or antifungal medications. Controlling further spread requires a rapid diagnosis. Assessment of clinical symptoms, histological analysis, serological testing, and pathogen culture are all necessary for the diagnosis of sporotrichosis. However, these procedures are unable to identify the species. The development of safe, reliable, and species-specific diagnostic techniques is essential. Objective: To establish and evaluate a new quantitative real-time PCR assay for the rapid diagnosis of sporotrichosis and to identify relevant species. Methods: Polymorphisms in calmodulin (CAL) gene sequences and the internal transcribed spacer (ITS) were used in a quantitative real-time PCR assay to identify S. globosa, S. schenckii, and non-target species. Results: The quantitative real-time PCR assay had 100% sensitivity and specificity. The limit of detection was 6 fg/µl. Thirty-four clinical specimens were verified to be infected with S. globosa with a 100% positive detection rate. Conclusions: The quantitative PCR technique developed in this study is a quick, accurate, and targeted method of identifying S. globosa based on polymorphisms in CAL sequences and ITS. It can be used for a prompt clinical diagnosis to identify S. globosa in clinical specimens from patients with sporotrichosis. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusionNeuroblastoma, a pediatric malignancy, is significantly influenced by genetic factors. Prior research indicates that the OGG1 rs1052133 G > C polymorphism correlates with a decreased risk of neuroblastoma.We analyzed 57 neuroblastoma and 21 adrenal samples, using immunohistochemistry to measure OGG1 and STUB1 expression levels. We conducted a survival analysis to explore relationship between the expressions and neuroblastoma prognosis.Notably higher OGG1 expression and significantly lower STUB1 expression in neuroblastoma. OGG1 levels were significantly correlated with patient age, tumor location, histological grade, Shimada classification, INSS stage, and risk category. A negative association was observed between OGG1 and STUB1 expressions. Higher OGG1 expression was linked to reduced PFS and OS. Lower STUB1 expression was associated with unfavorable PFS. Additionally, OGG1 expression and risk category emerged as independent predictors of prognosis.OGG1 potentially functions as an oncogene in NB, with its activity possibly modulated by STUB1 through the ubiquitination pathway. [ABSTRACT FROM AUTHOR]

Background: Atresia of the infrarenal inferior vena cava (IVC) is associated with thrombophilia and antithrombin (AT) deficiency (ATD) due to homozygosity for the so-called Budapest 3 variant, c.391C > T, in the gene, SERPINC1. Case presentation: We report on a father and his two sons that had severe thrombosis at a young age. One son had absence of, and the other had very gracile infrarenal IVC. The father had gracile vena iliaca. All had significant collateral building. AT activity was determined with four different methods and varied between moderately reduced and borderline normal values, depending on the method. While all were heterozygous for c.391C > T, the father was also heterozygous for a variant of uncertain significance in SERPINC1. Conclusions: The findings support the association between c.391C > T in SERPINC1, thrombophilia, and atresia of the IVC system and indicate that even heterozygosity for c.391C > T may contribute to such anomalies. ATD detection was hampered by the varying sensitivity of methods used for AT activity measurement. [ABSTRACT FROM AUTHOR]

Background: Migraine is a common primary headache that has a significant impact on patients' quality of life. The co-occurrence of migraine and depression is frequent, resulting in more complex symptoms and a poorer prognosis. The evidence suggests that depression and migraine comorbidity share a polygenic genetic background. Objective: The aim of this study is to identify related genetic variants that contribute to genetic susceptibility to migraine with and without depression in a Chinese cohort. Methods: In this case-control study, 263 individuals with migraines and 223 race-matched controls were included. Eight genetic polymorphism loci selected from the GWAS were genotyped using Sequenom's MALDI-TOF iPLEX platform. Results: In univariate analysis, ANKDD1B rs904743 showed significant differences in genotype and allele distribution between migraineurs and controls. Furthermore, a machine learning approach was used to perform multivariate analysis. The results of the Random Forest algorithm indicated that ANKDD1B rs904743 was a significant risk factor for migraine susceptibility in China. Additionally, subgroup analysis by the Boruta algorithm showed a significant association between this SNP and migraine comorbid depression. Migraineurs with depression have been observed to have worse scores on the Beck Anxiety Inventory (BAI) and the Migraine Disability Assessment Scale (MIDAS). Conclusion: The study indicates that there is an association between ANKDD1B rs904743 and susceptibility to migraine with and without depression in Chinese patients. [ABSTRACT FROM AUTHOR]

Macrophytes often live in fluvial backwaters that have a variety of hydrological connections to a main river. Since the ability of these plants to adapt to changing environments may depend on the genetic diversity of the populations, it is important to know whether it can be influenced by habitat characteristics. We examined the microsatellite polymorphism of the submerged macrophyte Ceratophyllum demersum from various backwaters and showed that the genetic diversity of this plant clearly reflects habitat hydrological differences. The greatest genetic variability was found in a canal system where constant water flow maintained a direct connection between the habitats and the river. In contrast, an isolated backwater on the protected side of the river had the lowest plant genetic diversity. Oxbows permanently connected to the branch system with static or flowing water, and former river branches temporarily connected to the main bed contained populations with moderately high or low genetic variability. The results demonstrate that habitat fragmentation can be a result not only of the loss of direct water contact, but also of the lack of flowing water. Adverse hydrological changes can reduce the genetic diversity of populations and thus the ability of this macrophyte to adapt to changing environments. [ABSTRACT FROM AUTHOR]

Puccinia graminis f. sp. tritici (Pgt), the causal agent of wheat stem rust, poses a significant threat to global wheat production. Genetic resistance offers a cost-effective and sustainable solution. The durum wheat landrace PI 94701 was previously hypothesized to carry two stem rust resistance (Sr) genes, but their chromosomal locations were unknown. In this study, we mapped and characterized an all-stage Sr gene in PI 94701, temporarily designated as SrPI94701. In seedling tests, SrPI94701 was effective against all six Pgt races tested. Using a large segregating population, we mapped SrPI94701 on chromosome arm 5BL within a 0.17-cM region flanked by markers pku69124 and pku69228, corresponding to 1.04 and 2.15 Mb genomic regions in the Svevo and Chinese Spring reference genomes. Within the candidate region, eight genes exhibited differential expression between the Pgt-inoculated resistant and susceptible plants. Among them, two nucleotide-binding leucine-rich repeat (NLR) genes, TraesCS5B03G1334700 and TraesCS5B03G1335100, showed high polymorphism between the parental lines and were upregulated in Pgt-inoculated resistant plants. However, the flanking and completely linked markers developed in this study could not accurately predict the presence of SrPI94701 in a survey of 104 wheat accessions. SrPI94701 is a promising resource for enhancing stem rust resistance in wheat breeding programs. [ABSTRACT FROM AUTHOR]

Age, ethnic background and genetic components have been identified as the established risks for prostate cancer (PCa). Pentraxin 3 (PTX3), originally identified as a pattern‐recognition molecule for defence against infectious agents, has multiple functions in tissue repair and in the regulation of cancer‐associated inflammation. In this study, we sought to investigate the impact of PTX3 gene variants on the development of PCa. Genotypes of four common single‐nucleotide polymorphisms (SNPs) of PTX3 gene, including rs1840680, rs2305619, rs3816527 and rs2120243, were profiled among 705 PCa patients and 705 ethnicity‐matched controls. In this study, we found that patients who carry at least one minor allele (C) of rs3816527 (AC and CC) tended to develop advanced forms of diseases (clinical large T stage, OR, 1.593, p = 0.032; pathologically‐confirmed nodal spread, OR, 1.987, p = 0.011; metastatic tumour, OR, 3.896, p = 0.032) as compared with those homologous for the major allele (AA). Further stratification analysis showed that such association of rs3816527 with lymphatic and distal metastasis of PCa was accentuated in the younger age group (≤65 at diagnosis) but not seen in the older age group (>65 at diagnosis), suggesting an age‐specific effect of PTX3 variants. Prediction of PTX3 protein structure implied that polymorphism may alter the quaternary organization and oligomerization of PTX3 protein. Moreover, our gene silencing experiments and survey of public datasets revealed that elevation of PTX3 levels in PCa was required for cell migration and associated with tumour metastasis. Our results highlight an association of PTX3 rs3816527 with the progression of PCa. [ABSTRACT FROM AUTHOR]

Preeclampsia is the main cause of maternal and infant mortality and morbidity during pregnancy. Killer cell immunoglobulin-like receptor 2DL4 (KIR2DL4) and human leukocyte antigen G (HLA-G) play crucial roles in immune tolerance at the maternal-fetal interface. In this case-control study, 154 maternal-fetal pairs were recruited, including 74 pairs with preeclampsia (56 of 74 pairs from family triads) and 80 pairs with a normal pregnancy (78 of 80 pairs from family triads). SNaPshot technology was used to detect genetic polymorphisms for 7 TagSNPs in the KIR2DL4 and HLA-G genes. Among the fetal HLA-G gene polymorphisms, rs9380142 (A vs. G: OR = 2.802, 95% CI = 1.761-4.458) and rs1063320 (G vs. C: OR = 1.807, 95% CI = 1.144-2.852) differed between the preeclampsia group and the control group. The transmission disequilibrium test (TDT) suggested that the differences in the rs9380142G/A polymorphism in foetuses between preeclampsia triads and control triads were due to differences in transmission from the parents (P = 0.001). There was no significant difference in the distribution of maternal KIR2DL4 alleles or genotype frequency between the preeclampsia group and the control group. Gene-gene interaction analysis revealed that the combined genotypes of maternal rs649216-CC and fetal rs9380142-GG, maternal rs1051456-CG/GG and fetal rs9380142-GG, maternal rs34785252-CC and fetal rs9380142-AA/GA, and maternal rs34785252-CC/AA and fetal rs9380142-GG were associated with a significantly lower risk of preeclampsia. Therefore, this study suggested that the combination of maternal KIR2DL4 and fetal HLA-G polymorphisms was associated with preeclampsia in a Han Chinese population. [ABSTRACT FROM AUTHOR]

Oxytocin receptor gene polymorphism (OXTR rs53576) is associated with human social cognition and behavior. However, results on the contribution of OXTR rs53576 to individual differences in depressive symptoms have been inconsistent. This meta-analysis examined the association between OXTR rs53576 and depressive symptoms and under what conditions this association might hold true. A systematic search of PubMed, PsycInfo, and Web of Science was performed for English articles describing human-based studies from the inception of the databases to February 2023, as well as a manual search of the reference lists of the included articles. The search terms included OXTR rs53576, depressive symptoms, and their synonyms. Standardized mean differences in depressive symptoms between individuals classified by OXTR rs53576 genotypes were evaluated, and random-effects meta-analyses were performed. A total of 10 studies including 2972 subjects from six countries were pooled. Results provided no evidence of an association between OXTR rs53576 and depressive symptoms. The between-study differences in I2 statistics by ethnicity, disease history, and age group suggested the presence of moderating variables. However, the number of eligible studies was small with considerable heterogeneity. Findings underscore the importance of homogeneous sampling for research on depression genetics to affirm the association between OXTR rs35376 and depressive symptoms. [ABSTRACT FROM AUTHOR]

The present study examined the genetic diversity of two populations of Dotilla myctiroides (Milne-Edwards) from Peninsular Malaysia. Based on 640-bp COX1 (cytochrome c oxidase subunit 1) gene sequences, the D. myctiroides specimens from Peninsular Malaysia, Singapore and India formed a lineage which was distinctly separated from Dotilla wichmanni and D. fenestrata. Sixteen COX1 haplotypes were found in Peninsular Malaysia samples, with 11 haplotypes in the Morib sample, eight in the Tanjung Tuan sample, and three common haplotypes in these samples. The Singapore specimen had the commonest haplotype of Peninsular Malaysia, while the Indian specimen had a distinct haplotype. The proportions of the two most common COX1 haplotypes were not significantly different between the Morib and Tanjung Tuan samples. The difference in the mean haplotype diversity between these samples was statistically significant. However, the nucleotide diversity of the two samples was not significantly different and there was no genetic subdivision/differentiation between the two populations. The high number of closely related haplotypes indicates the possibility of a recent population expansion. The data provide valuable information for future studies on the genetic diversity, population structure and phylogeography of Dotilla species. [ABSTRACT FROM AUTHOR]

Background: Esophageal cancer is the eleventh most common cancer and is the seventh leading cause of mortality worldwide. Vascular endothelial growth factor (VEGF) and its receptors pathway are a key regulator of angiogenesis and play an important role in carcinogenesis. The aim of current study was to evaluate the association of five VEGFR polymorphisms with esophageal cancer risk in patients from Punjab, North-west India. Methods: This case–control study included 310 esophageal cancer patients and 325 age and gender matched healthy controls. VEGFR1-710C/T, VEGFR2-604 T/C (rs2071559), VEGFR2 1192 G/A (rs2305948), VEGFR2 1719A/T (rs1870377) and VEGFR3 (rs72816988) polymorphisms were genotyped by using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) method. Restriction digestion products were analyzed on 2.4% agarose gel and genotype was assigned to each sample on the basis of fragments obtained after digestion. Randomly 10% samples were repeated by Sanger sequencing to revalidate the results. Results: There was a significant association of CT genotype (OR = 0.28; 95%CI, 0.10–0.76; p = 0.01) and T allele (OR = 0.28; 95%CI, 0.10–0.77; p = 0.01) of VEGFR1-710C/T polymorphism with decreased risk of esophageal cancer. TC genotype of VEGFR2-604 T/C (OR = 0.66; 95%CI, 0.44–0.97; p = 0.03) and GA genotype of VEGFR2 1192G/A (OR = 0.54; 95%CI, 0.31–0.95; p = 0.03) polymorphisms were significantly associated with decreased risk of esophageal cancer. There was no significant difference in allele and genotype frequency of VEGFR2 1719A/T and VEGFR3 (rs72816988) polymorphisms between esophageal cancer patients and controls (p > 0.05). Haplotype analysis revealed that haplotype C-604A1719A1192 was significantly associated with the decreased esophageal cancer risk (OR = 0.44; 95%CI, 0.23–0.84; p = 0.01). Conclusion: VEGFR1-710C/T, VEGFR2-604 T/C and VEGFR2 1192G/A polymorphisms were associated with the decreased risk of esophageal cancer in patients from Punjab, North-west India. [ABSTRACT FROM AUTHOR]

The prevalence of HCV infection in Egypt has decreased following the introduction of direct-acting antiviral therapy. However, treatment response is influenced by various factors, particularly host immunogenetics such as IL-28B and FOXP3 polymorphisms. The current study examined the impact of SNPs in the FOXP3 gene promoter region on HCV-infected Egyptian patients, along with SNPs in the IL28B gene.This study involved 99 HCV patients who achieved SVR12 after a 12 week DAA treatment while 63 HCV patients experienced treatment failure. IL28B rs12979860 SNP was identified using real-time PCR, while IL28B rs8099917, FOXP3 rs3761548, and rs2232365 SNPs were analyzed using RFLP-PCR. Serum levels of IL28B and FOXP3 were quantified using ELISA technique in representative samples from both groups. The IL28B rs12979860 T > C (P = 0.013) and FOXP3 rs2232365 A > G polymorphisms (P = 0.008) were found to significantly increase the risk of non-response. Responders had higher IL28B serum levels (P = 0.046) and lower FOXP3 levels (P < 0.001) compared to non-responders. Regression analysis showed an association between IL28B rs12979860 and FOXP3 rs2232365 with treatment response, independent of age and gender. A predictive model was developed with 76.2% sensitivity and 91.9% specificity for estimating DAAs response in HCV patients.Our findings confirmed the IL28B rs12979860 T > C and FOXP3 rs2232365 A > G polymorphisms significantly affect DAA treatment response in HCV Egyptian patients. Lower levels of IL-28B along with higher levels of FOXP3 are linked to poor response. Our results may lead to new insights into DAA responsiveness contributing to personalized medicine and improving therapeutic decision-making for HCV patients. [ABSTRACT FROM AUTHOR]

Premise Methods Results Discussion There is a general lack of consensus on the best practices for filtering of single‐nucleotide polymorphisms (SNPs) and whether it is better to use SNPs or include flanking regions (full “locus”) in phylogenomic analyses and subsequent comparative methods.Using genotyping‐by‐sequencing data from 22 Glycine species, we assessed the effects of SNP vs. locus usage and SNP retention stringency. We compared branch length, node support, and divergence time estimation across 16 datasets with varying amounts of missing data and total size.Our results revealed five aspects of phylogenomic data usage that may be generally applicable: (1) tree topology is largely congruent across analyses; (2) filtering strictly for SNP retention (e.g., 90–100%) reduces support and can alter some inferred relationships; (3) absolute branch lengths vary by two orders of magnitude between SNP and locus datasets; (4) data type and branch length variation have little effect on divergence time estimation; and (5) phylograms alter the estimation of ancestral states and rates of morphological evolution.Using SNP or locus datasets does not alter phylogenetic inference significantly, unless researchers want or need to use absolute branch lengths. We recommend against using excessive filtering thresholds for SNP retention to reduce the risk of producing inconsistent topologies and generating low support. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusionsThis study aims to explore the association between variations in the Surfactant Protein-B (SFTPB) gene and the risk of neonatal respiratory distress syndrome (NRDS).A comprehensive literature search was conducted across PubMed, Scopus, EMBASE, and CNKI databases up to February 10, 2024, to identify pertinent studies.A total of seventeen studies examining the +1580 C/T polymorphism (2,058 cases and 2,596 controls) and five studies investigating the −18 A/C polymorphism (680 cases and 739 controls) were included in the analysis. The pooled data indicated that the +1580 C/T polymorphism confers a protective effect against NRDS in various populations and ethnic groups. Conversely, the −18 A/C polymorphism did not demonstrate a significant association either globally or among Asian neonates.The +1580 C/T variant appears to be protective against NRDS, whereas the −18 A/C polymorphism shows minimal impact on the disease’s progression. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions Sunitinib exhibits considerable interindividual variability in exposure. While the target total plasma concentration of sunitinib and its active metabolite is 50–87.5 ng/mL for the intermittent dosing schedule, ~10–21% of patients experience higher exposures (>87.5 ng/mL), correlated with an increased risk for toxicity. Previous research identified single nucleotide variants (SNVs) in genes from the sunitinib pharmacokinetic pathway to be associated with efficacy and toxicity. However, significant interindividual variability in exposure remains unexplained. Our aim was to identify genetic variants associated with supratherapeutic exposure of sunitinib.This was a genome‐wide association study. Cases were identified during routine therapeutic drug monitoring and consisted of patients with dose‐normalized sunitinib plasma concentrations >87.5 ng/mL (intermittent dosing) or >75 ng/mL (continuous dosing). Controls were sampled from the historical cohort EuroTARGET who tolerated the standard dose of 50 mg in an intermittent schedule. SNVs were tested for an association with sunitinib exposure. A P‐value ≤5 × 10−8 was considered significant and a P‐value between 5 × 10−8 and 5 × 10−6 was considered suggestive.Sixty‐nine cases and 345 controls were included for association analysis. One SNV (rs6923761), located on the gene glucagon‐like peptide 1 receptor, was significantly associated with increased sunitinib exposure (P = 7.86 × 10−19). Twelve SNVs were suggestive for an association with sunitinib exposure (P ≤ 5 × 10−6).While rs6923671 is associated with high sunitinib exposure, the underlying mechanism is not yet clarified and warrants further investigation. We could not confirm the earlier found associations between SNVs in candidate genes involved in the pharmacokinetic pathway of sunitinib and its efficacy and toxicity. [ABSTRACT FROM AUTHOR]

Background: Ventricular septal defect (VSD) is the most common congenital heart disease. Although a small number of genes associated with VSD have been found, the genetic factors of VSD remain unclear. In this study, we evaluated the association of 10 candidate single nucleotide polymorphisms (SNPs) with isolated VSD in a population from Southwest China. Methods: Based on the results of 34 congenital heart disease whole-exome sequencing and 1000 Genomes databases, 10 candidate SNPs were selected. A total of 618 samples were collected from the population of Southwest China, including 285 VSD samples and 333 normal samples. Ten SNPs in the case group and the control group were identified by SNaPshot genotyping. The chi-square (χ2) test was used to evaluate the relationship between VSD and each candidate SNP. The SNPs that had significant P value in the initial stage were further analysed using linkage disequilibrium, and haplotypes were assessed in 34 congenital heart disease whole-exome sequencing samples using Haploview software. The bins of SNPs that were in very strong linkage disequilibrium were further used to predict haplotypes by Arlequin software. ViennaRNA v2.5.1 predicted the haplotype mRNA secondary structure. We evaluated the correlation between mRNA secondary structure changes and ventricular septal defects. Results: The χ2 results showed that the allele frequency of FLT4 rs383985 (P = 0.040) was different between the control group and the case group (P < 0.05). FLT4 rs3736061 (r2 = 1), rs3736062 (r2 = 0.84), rs3736063 (r2 = 0.84) and FLT4 rs383985 were in high linkage disequilibrium (r2 > 0.8). Among them, rs3736061 and rs3736062 SNPs in the FLT4 gene led to synonymous variations of amino acids, but predicting the secondary structure of mRNA might change the secondary structure of mRNA and reduce the free energy. Conclusions: These findings suggest a possible molecular pathogenesis associated with isolated VSD, which warrants investigation in future studies. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethods and resultsConclusionCoronary artery spasm is among the etiology of myocardial infarction. Oxidative stress is involved in the pathogenesis of coronary artery spasm (CAS). Paraoxonase-1 (PON1) is an HDL-bound antioxidant enzyme that protects LDL from oxidative modification. Oxidative-stress-related genetic factors and certain polymorphisms in the paraoxonase 1 gene might influence the pathogenesis of CAS. We aimed to investigate the association between PON1 gene polymorphism and its enzymatic activity and coronary artery spasm during cardiac catheterization.The study population was 150 patients who underwent elective coronary angiography. Subjects were genotyped to the Q192R polymorphism (rs662) on the PON1 gene by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and PON1 activity was quantitatively analyzed by enzyme linked immunosorbent assay. Results showed that the subjects carrying the RR genotype and R allele were significantly more likely to develop coronary artery spasm (OR=4.2, 2.03, P< 0.006, P˂0.02, respectively). Moreover, serum PON1 levels were significantly decreased (P˂0.001) in the CAS group. RR genotype of PON1 Q192R polymorphism, Tc, LDLc, TG, catheter size, and paroxonase-1 serum level are independent predictors of coronary spasm.We conclude that the PON1 (rs662) gene polymorphism is associated with CAS during cardiac catheterization in Egyptians. The PON1-192R allele and lower serum enzyme concentration may play an important role in coronary spasm. [ABSTRACT FROM AUTHOR]