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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]

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: 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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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: 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]

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]

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]

Methotrexate is a widely used drug in clinical practice for the treatment of collagen vascular diseases and malignant tumors. It has good anti-inflammatory and anti-proliferative effects, but the cytotoxicity of methotrexate can cause various adverse reactions in patients. Studies have shown that the sensitivity and tolerance of different individuals to methotrexate is different. There are many reasons for this difference. Among them, genetic polymorphism is one of the main factors that cause individual differences. This article provides an overview of the genetic polymorphisms of key proteins involved in methotrexate metabolism and transport, such as MTHFR, FPGS, γ-GGH, ABC transporter, OATPs, SLC, TS and DHFR, are related to their efficacy and adverse reactions. The aim is to clarify the impact of genetic polymorphisms on the efficacy and adverse effects of methotrexate at the pharmacogenomic level, in order to provide a basis for the clinical application of methotrexate. [ABSTRACT FROM AUTHOR]

Scrapie is a transmissible spongiform encephalopathy affecting sheep and goats. The prion protein-encoding gene (PRNP) plays a crucial role in determining susceptibility and resistance to scrapie. At the European level, surveillance of scrapie is essential to prevent the spread of the disease to livestock. According to the Regulation EU 2020/772 polymorphisms K222, D/S146 could function as resistance alleles in the genetic management of disease prevention. In Italy, a breeding plan for scrapie eradication has not been implemented for goats. However, surveillance plans based on the PRNP genotype have been developed as a preventive measure for scrapie. This research aimed to describe the polymorphisms at 7 positions within the PRNP gene in 956 goats of the Alpine, Saanen and mixed populations farmed in the Lombardy Region in Italy. PRNP polymorphisms were detected using single nucleotide polymorphism markers included in the Neogen GGP Goat 70 k chip. The K222 allele occurred in all populations, with frequencies ranging from 2.1 to 12.7%. No animals carried the S/D146 resistance allele. However, it has been demonstrated that polymorphisms in the other positions analysed could influence resistance or susceptibility to scrapie outbreaks in different ways. Ten potentially distinct haplotypes were found, and the most prevalent of the three populations was H2, which differed from the wild type (H1) in terms of mutation (S vs P) at codon 240. This study provided additional information on the genetic variability of the PRNP gene in these populations in the Lombardy region of Italy, contributing to the development of genetic control measures for disease prevention. [ABSTRACT FROM AUTHOR]

Impulse control disorders and their consequences display variability among individuals, indicating potential involvement of environmental and genetic factors. In this retrospective study, we analyzed a cohort of Parkinson's disease patients treated with dopamine agonists and investigated the influence of the dopamine D4 receptor gene polymorphism, DRD4 7R+, which is linked to psychiatric disorders, impulsive traits, and addictive behaviors. We found that DRD4 7R+ is a significant genetic risk factor associated with the severity of ICD. [ABSTRACT FROM AUTHOR]

Folate-mediated one-carbon metabolism (FOCM) plays an important role in colorectal carcinogenesis. Previous studies have assessed the role of folate-mediated one-carbon metabolism (FOCM)-related gene-diet interaction in the aetiology of colorectal cancer (CRC), however, the results remained inconclusive. Thus, this study aimed to investigate dietary factors and genetic variants related to FOCM, as well as potential nutrient-gene and nutrient-lifestyle interactions, on CRC risk. This observational study included 229 patients diagnosed with CRC and 229 age- and sex-matched subjects as controls from a population-based bowel cancer screening program. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95%CI) for CRC risk. A Bonferroni-corrected threshold of α = 0.005 was considered significant, and P values less than 0.05 were considered to be suggestive of an association. After Bonferroni correction, a high dietary intake of betaine was associated with a decreased risk of CRC in the adjusted model (OR, 95% CI: 0.21, 0.10–0.40, P < 0.001). Two SNPs, rs1476413 and rs17824591, exhibited significant gene-diet interactions with total choline ad vitamin B12 intakes, respectively, in adjusted models (total choline, tertile 3 vs. 1, OR, 95% CI: 0.25, 0.11–0.66, Pinteraction = 0.012; vitamin B12, tertile 2 vs. tertile 1, OR, 95% CI: 2.48, 1.04-5.00, Pinteraction = 0.003). These findings suggest that betaine intake and interactions between some dietary factors and variants in MTHFR and MTHFD1 genes have an influence on CRC risk in the population studied. If these results are confirmed, specific nutritional intervention strategies could be designed. [ABSTRACT FROM AUTHOR]

Rice quality has a major impact on its economic value, necessitating the breeding of high-quality grain varieties. In addition, varieties with superior germination and growth at low temperatures are required for direct sowing, which enables the low-cost production of rice. We developed Akikei770, a near-isogenic line from the high-quality, good-tasting cultivar Akitakomachi, carrying the qLTG3-1 gene from the Maratelli cultivar, which enhances low-temperature germinability. Although Akikei770 exhibited improved low-temperature germinability, it was inferior to Akitakomachi in appearance quality of brown rice and in eating quality of cooked rice. In Akikei770, a short arm region of up to 222 kb on chromosome 3 from Maratelli was introgressed, and only the qLTG3-1 gene exhibited polymorphisms within the coding region compared to Akitakomachi. The qLTG3-1 genotype was significantly associated with brown rice quality in the F2 population, which indicates that the qLTG3-1 gene was involved in this trait with no involvement of other chromosomal regions of Akikei770. The functional qLTG3-1 allele in Akikei770, encoding a hybrid glycine-rich protein (HyGRP) that is localized on the cell wall or membrane, enhanced the low-temperature germinability. Because a loss-of-function allele of qLTG3-1 increased the appearance quality of brown rice in a recessive manner, it was concluded that HyGRP, which enhances low-temperature germinability, has a pleiotropic effect that reduces the appearance quality of brown rice. [ABSTRACT FROM AUTHOR]

Persimmon is classified as either pollination-constant non-astringent (PCNA) or non-PCNA on the basis of the loss of astringency in fruit. PCNA trait of persimmon has attracted much research attention owing to its economical merit, as there is no cost in removing astringency. To efficiently develop new PCNA cultivars in crossbreeding, marker-assisted selection plays a crucial role. Here, we describe a cleaved amplified polymorphic sequence (CAPS) marker that can be used to select PCNA persimmon. A sequence-characterized amplified region (SCAR) marker used to screen for PCNA offspring is unsuitable for populations recently derived from two non-PCNA parents ('Yoshidagosho' and 'Toyoichi'), resulting in the selection of non-PCNA offspring as PCNA. To detect specific polymorphisms for these non-PCNA offspring, we analyzed fragment sizes of SCAR marker products by capillary DNA sequencing. A slightly lower-molecular-weight fragment at 353 bp was specifically detected in non-PCNA offspring but not in PCNA offspring. We treated the SCAR marker products with the StuI restriction enzyme and demonstrated that the smaller 353-bp fragment corresponded to allele a353-1, one of four previously identified sequence polymorphisms at the 353-bp peak, and a353-1 is linked to non-PCNA trait. Comprehensive analysis of 130 germplasms by the CAPS marker, detecting the truncated fragment after StuI treatment, indicated the presence of a353-1 in 38 non-PCNA cultivars. Our findings suggest the potential use of the CAPS marker for selecting PCNA offspring derived from these 38 non-PCNA cultivars. [ABSTRACT FROM AUTHOR]

Background: Hypoxia is often involved in tumor microenvironment, and the hypoxia‐induced signaling pathways play a key role in aggressive cancer phenotypes, including angiogenesis, immune evasion, and therapy resistance. However, it is unknown what role genetic variants in the hypoxia‐related genes play in survival of patients with non‐small cell lung cancer (NSCLC). Methods: We evaluated the associations between 16,092 single‐nucleotide polymorphisms (SNPs) in 182 hypoxia‐related genes and survival outcomes of NSCLC patients. Data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial were used as the discovery dataset, and the Harvard Lung Cancer Susceptibility (HLCS) Study served as the replication dataset. We also performed additional linkage disequilibrium analysis and a stepwise multivariable Cox proportional hazards regression analysis in the PLCO dataset. Results: An independent SNP, ERRFI1 rs28624 A > C, was identified with an adjusted hazards ratio (HR) of 1.31 (95% CI = 1.14–1.51, p = 0.0001) for overall survival (OS). In further analyses, unfavorable genotypes AC and CC, compared with the AA genotype, were associated a worse OS (HR = 1.20, 95% CI = 1.03–1.39, p = 0.014) and disease‐specific survival (HR = 1.21, 95% CI = 1.04–1.42, p = 0.016). Further expression quantitative trait loci analysis indicated that ERRFI1 rs28624C genotypes were significantly associated with higher ERRFI1 mRNA expression levels in the whole blood. Additional analysis showed that high ERRFI1 mRNA expression levels were associated with a worse OS in patients with lung adenocarcinoma. Conclusion: Our findings suggest that genetic variants in the hypoxia‐related gene ERRFI1 may modulate NSCLC survival, potentially through their effect on the gene expression. [ABSTRACT FROM AUTHOR]

The main objective of mapping quantitative trait loci (QTL) and genome-wide association studies (GWAS) is to identify and locate QTLs on the genome. Estimating the sizes of QTL is equally important as identifying the QTLs. The size of a QTL is often measured by the QTL variance, or the proportion of phenotypic variance explained by the QTL, known as the QTL heritability. The reported QTL heritability is biased upward for small-sized QTLs estimated from small samples, especially in GWAS with a very small P -value threshold accommodating to Bonferroni correction for multiple tests. The phenomenon is called the Beavis effect. Methods of correcting the Beavis effect have been developed for additive effect models. Corresponding methods are not available for QTLs with more than one effect, such as QTLs including dominance and other genetic effects. In this study, we developed explicit formulas for estimating the variances and heritability for QTL with multiple effects. We also developed a method to remove nuisance parameters via an annihilator matrix. Finally, biases in estimated QTL variances caused by the Beavis effect are investigated and corrected. The new method is demonstrated by analyzing the 1000 grain weight (KGW) trait in a hybrid rice population. [ABSTRACT FROM AUTHOR]

Background and Aim: We previously identified that ever‐smoking and severe gastric atrophy in pepsinogen are risk factors for synchronous gastric cancers (SGCs). This study aimed to determine the association of alcohol drinking status or alcohol‐related genetic polymorphism with SGCs and also stratify their risk. Methods: This multi‐center prospective cohort study included patients who underwent endoscopic submucosal dissection for the initial early gastric cancers at 22 institutions in Japan. We evaluated the association of alcohol drinking status or alcohol dehydrogenase 1B (ADH1B) and acetaldehyde dehydrogenase 2 (ALDH2) genotypes with SGCs. We then stratified the risk of SGCs by combining prespecified two factors and risk factors identified in this study. Results: Among 802 patients, 130 had SGCs. Both the ADH1B Arg and ALDH2 Lys alleles demonstrated a significant association with SGCs on multivariate analysis (odds ratio, 1.77), although alcohol drinking status showed no association. The rates of SGCs in 0–3 risk factors in the combined evaluation of three risk factors (ever‐smoking, severe gastric atrophy in pepsinogen, and both the ADH1B Arg and ALDH2 Lys alleles) were 7.6%, 15.0%, 22.0%, and 32.1%, respectively. The risk significantly increased from 0 to 3 risk factors on multivariate analysis (P for trend <0.001). Conclusions: Both the ADH1B Arg and ALDH2 Lys alleles were at high risk for SGCs. The risk stratification by these three factors may be a less invasive and promising tool for predicting their risk. [ABSTRACT FROM AUTHOR]

Simple Summary: Genetic diversity plays a crucial role in determining the ability of populations to evolve. We investigated the genetic variation of the black-and-white snub-nosed monkey by integrating adaptive MHC genes and neutral microsatellites. We found that neutral loci exhibited high heterozygosity and a high degree of polymorphism, while MHC genes showed high heterozygosity and moderate polymorphism. Additionally, positive selection and trans-species evolution indicated that historical balancing selection might have sustained the MHC polymorphism. This study provides valuable scientific evidence and a reference for formulating or amending conservation strategies for black-and-white snub-nosed monkeys. Genetic diversity is an essential indicator that echoes the natural selection and environmental adaptation of a species. Isolated small populations are vulnerable to genetic drift, inbreeding, and limited gene flow; thus, assessing their genetic diversity is critical in conservation. In this study, we studied the genetic diversity of black-and-white snub-nosed monkeys (Rhinopithecus bieti) using neutral microsatellites and five adaptive major histocompatibility complex (MHC) genes. Two DQA1 alleles, two DQB1 alleles, two DRB1 alleles, two DRB5 alleles, and three DPB1 alleles were isolated from a population. The results indicate that neutral microsatellites demonstrate a high degree of heterozygosity and polymorphism, while adaptive MHC genes display a high degree of heterozygosity and moderate polymorphism. The results also show that balancing selection has prominently influenced the MHC diversity of the species during evolution: (1) significant positive selection is identified at several amino acid sites (primarily at and near antigen-binding sites) of the DRB1, DRB5, and DQB1 genes; (2) phylogenetic analyses display the patterns of trans-species evolution for all MHC loci. This study provides valuable genetic diversity insights into black-and-white snub-nosed monkeys, which dwell at the highest altitude and have experienced the harshest environmental selection of all primates globally since the Pleistocene. Such results provide valuable scientific evidence and a reference for making or amending conservation strategies for this endangered primate species. [ABSTRACT FROM AUTHOR]

Background: Over the past few decades, a number of studies have linked vitamin-D deficiency with ED (Erectile dysfunction) risk factors. There is a clear correlation between VD (vitamin-D) levels and ED, according to observational and interventional researches that have been reported in the literature. This crucial information encouraged scientists to investigate the impact of VD on erectile function in greater detail. The fact that vitamin D is a component of a healthy penis that begins in early life has just come to light, however there haven't been many research looking at the connection between vitamin D receptor gene polymorphism and erectile dysfunction. Objective: To evaluate the relationship between arteriogenic erectile dysfunction and the vitamin D receptor gene polymorphism. Subjects and Methods: Between October 2022 and October 2023, at Al-Azhar University Hospitals, 40 patients with arteriogenic ED and 40 healthy controls underwent informed consent, a detailed history, a physical examination, a penile duplex ultrasound and the extraction of peripheral blood to determine the type of polymorphism for each of the vitamin D receptors: FokI, BsmI, ApaI and TaqI by polymerase chain reaction (PCR). Results: There is no statistically significant association between arteriogenic erectile dysfunction and the vitamin D receptors (VDR) gene polymorphisms FokI, BsmI, ApaI and TaqI. Conclusion: Since there is no statistically significant association between the polymorphism of the vitamin D receptor (VDR) gene and arteriogenic erectile dysfunction, it is advised to investigate other VDR gene polymorphisms as well as alternative clinical subtypes of erectile dysfunction. [ABSTRACT FROM AUTHOR]

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody production and diverse tissue and organ inflammatory affections. Interleukin 21 (IL-21) is implicated in B cell survival, proliferation, differentiation, class switching, and immunoglobulin production; therefore, it is considered a key cytokine in the pathogenesis of SLE. However, its association with disease activity and clinical phenotypes remains unclear. We aimed to evaluate the association of IL-21 levels with the disease activity and clinical phenotypes in patients with SLE. Also, we analyzed the IL21 polymorphisms associated with increased IL-21 levels. Methods: The IL-21 serum levels were determined using the enzyme-linked immunosorbent assay (ELISA) method. The rs2221903 and rs2055979 polymorphisms were assessed in 300 healthy controls (HCs) and 300 patients with SLE by the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) technique. The levels of IL-21 were monitored during follow-up visits in 59 patients with SLE. Results: The patients with SLE showed higher IL-21 levels compared to the HCs. The IL-21 levels did not correlate with Mex-SLEDAI and were not different in patients with inactive, mild–moderate, and severe disease. The IL-21 levels were increased in patients with hematological affection. The ROC curve analysis revealed that the IL-21 levels had good predictive power in discriminating among patients with SLE and HCs. In a follow-up analysis, the levels of IL-21 remained higher in the patients with SLE even when the patients were in remission. Also, the rs2221903 polymorphism was associated with increased IL-21 levels. Conclusions: This study highlights the importance of IL-21 as a key cytokine in SLE. IL-21 levels are higher in patients with SLE and remain increased regardless of disease activity. According to the ROC analysis, IL-21 is a potential biomarker of SLE. Further longitudinal studies are needed to explore the relationship between IL-21 and the clinical phenotypes of SLE. [ABSTRACT FROM AUTHOR]

Background: A glioma is a form of tumor that is abundant in blood vessels. Vascular endothelial growth factor receptor (VEGFR) and its receptor 2 (VEGFR2) are important in the process of angiogenesis. The relationship between VEGFR2 rs2071559 and glioma development is currently uncertain. The present study aims to analyze the correlation between VEGFR2 rs2071559 gene polymorphism and the susceptibility to gliomas. Methods: A thorough search was carried out in the Cochrane Library, Scopus, and Medline databases from inception until 20 February 2024 using a mix of pertinent keywords. We used random-effects models to examine the odds ratio (OR) and reported the results together with their respective 95% confidence intervals (CIs). Results: A total of six studies were incorporated. The results of our meta-analysis indicated that all genetic models of VEGFR2 rs2071559 gene polymorphism, starting from dominant (OR 1.40; p < 0.00001), recessive (OR 1.52; p < 0.0001), CC genotype (OR 1.78; p < 0.00001), CT genotype (OR 1.30; p < 0.0001), and C allele (OR 1.41; p < 0.00001), were associated with a higher risk of developing gliomas. The subgroup analysis revealed a higher OR for studies with a sample size of ≥500, originated from Asia, with a mean age of ≥42.3 years, and a male prevalence of <57%. Conclusions: This study suggests that VEGFR2 rs2071559 gene polymorphism is associated with a higher risk of gliomas. [ABSTRACT FROM AUTHOR]

Background: Among Egyptian females, hepatocellular carcinoma (HCC) ranks sixth, while among males it ranks second. The X-ray repair crosscomplementing group1 (XRCC1) could play a crucial role in reparation of oxidative DNA damage. An association was revealed between the risk of HCC and the genotypes and allele distribution of XRCC1 variants. Objectives: This research aimed at the evaluation of the relationship between XRCC1 gene polymorphism and the development of HCC among Egyptian patients who had HCV related cirrhosis. Patients and methods: This study recruited 93 individuals, including 31 apparently healthy subjects taken as controls (Group I), 31 cirrhotic patients with chronic hepatitis C virus (HCV) infection (Group II), and 31 HCC patients with HCV related cirrhosis (Group III). Xrcc1 gene polymorphism c.1517 G>C was determined using Polymerase Chain Reaction-Restricted Fragment Length Polymorphism (PCR-RFLP). Results: CC genotype was significantly increased (p=0.04) among HCC patients with HCV related cirrhosis (48.4%) compared to controls (12.9%). Also, C allele was significantly higher (p=0.01) among HCC patients (59.7%) compared to both cirrhotic patients (41.9%) and controls (33.9%). HCC patients had CC genotype 5.83 times more when compared to controls (OR=5.83, 95% CI= 1.46-23.3). HCC patients had C allele 2.89 times more when compared to controls (OR= 2.89, 95% CI= 1.39-6). The frequencies of (GC+CC) genotypes when combined were higher in HCC patients (71%) compared to both cirrhotic patients (58.1%) and controls (54.8%). Conclusion: The polymorphism of XRCC1 c.1517G>C was found to be associated with increased risk of HCC among patients with HCV related cirrhosis, besides; C allele had higher risk of HCC. [ABSTRACT FROM AUTHOR]

Aerobic exercise promotes uncoupling protein-1 (UCP-1) induced white adipose tissue browning by increasing serum nitric oxide (NO), irisin and interleukin-6 (IL-6). However, oxidative stress (OS) occurring during anaerobic exercise downregulates UCP-1. Moreover, UCP-1-3826 A/G polymorphism (UCP1P) is associated with weight gain due to impaired thermogenesis which may be due to UCP1P induced modification in OS. Therefore, our purpose was to investigate the role of UCP1P on the effects of acute maximal exercise (AME) and chronic anaerobic exercise (CAT) on serum OS, UCP-1, NO, irisin and IL-6 levels. Sport group (SG, n = 43) was formed of anaerobic athletes, while control group (CG, n = 43) comprised physically inactive men. Postprandial blood was taken from SG and CG before and after AME to determine serum UCP-1, irisin, IL-6, NO, and oxidative stress index (OSI = total oxidant/antioxidant status [TOS/TAS] ratio). To investigate the effects of CAT on serum parameters, SG and CG's results were compared. UCP1P was determined by restriction fragment length polymorphism analysis. AME significantly increased all parameters in SG and CG (P < 0.05). However, CAT increased only OSI and IL-6 (P < 0.05), decreased UCP-1 and TAS and did not affect TOS, NO and irisin. OSI of GG homozygous athletes were significantly higher than other genotype groups (P < 0.05). Although significant negative correlations were found between UCP-1 and OS markers in GG and AA genotype groups before AME, significant positive correlations were found between UCP-1 and TAS in AA genotype group after AME. GG homozygous athletes may be more prone to higher OS. Decrease in UCP-1 due to CAT may be affected by GG genotype group's genetic disposition for OS. [ABSTRACT FROM AUTHOR]

Objectives Primaquine is essential for the radical cure of Plasmodium vivax malaria and must be metabolized into its bioactive metabolites. Accordingly, polymorphisms in primaquine-metabolizing enzymes can impact the treatment efficacy. This pioneering study explores the influence of monoamine oxidase-A (MAO-A) on primaquine metabolism and its impact on malaria relapses. Methods Samples from 205 patients with P. vivax malaria were retrospectively analysed by genotyping polymorphisms in MAO-A and cytochrome P450 2D6 (CYP2D6) genes. We measured the primaquine and carboxyprimaquine blood levels in 100 subjects for whom blood samples were available on the third day of treatment. We also examined the relationship between the enzyme variants and P. vivax malaria relapses in a group of subjects with well-documented relapses. Results The median carboxyprimaquine level was significantly reduced in individuals carrying low-expression MAO-A alleles plus impaired CYP2D6. In addition, this group experienced significantly more P. vivax relapses. The low-expression MAO-A status was not associated with malaria relapses when CYP2D6 had normal activity. This suggests that the putative carboxyprimaquine contribution is irrelevant when the CYP2D6 pathway is fully active. Conclusions We found evidence that the low-expression MAO-A variants can potentiate the negative impact of impaired CYP2D6 activity, resulting in lower levels of carboxyprimaquine metabolite and multiple relapses. The findings support the hypothesis that carboxyprimaquine may be further metabolized through CYP-mediated pathways generating bioactive metabolites that act against the parasite. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions Abundant data are available on the effect of the A118G (rs1799971) single‐nucleotide polymorphism (SNP) of the μ‐opioid receptor OPRM1 gene on morphine and fentanyl requirements for pain control. However, data on the effect of this SNP on intraoperative remifentanil requirements remain limited. We investigated the effect of this SNP on intraoperative remifentanil requirements.We investigated 333 Japanese women, aged 21–69 years, who underwent laparoscopic gynecological surgery for benign gynecological disease under total intravenous anesthesia at Juntendo University Hospital. Average infusion rates of propofol and remifentanil during anesthesia and the average bispectral index (BIS) during surgery were recorded. Associations among genotypes of the A118G and phenotypes were examined with the Mann–Whitney U test.The average propofol infusion rate was not different between patients with different genotypes. The average remifentanil infusion rate was significantly higher in patients with the AG or GG genotype than the AA genotype (p = 0.028). The average intraoperative BIS was significantly higher in patients with the GG genotype than the AA or AG genotype (p = 0.039).The G allele of the A118G SNP was associated with higher intraoperative remifentanil requirements and higher intraoperative BIS values but was not associated with propofol requirements. Given that remifentanil and propofol act synergistically on the BIS, these results suggest that the G allele of the A118G SNP is associated with lower effects of remifentanil in achieving adequate intraoperative analgesia and in potentiating the sedative effect of propofol on the BIS. [ABSTRACT FROM AUTHOR]

The objective of this study is to explore the relationship between the vascular endothelial growth factor (VEGF)+936 C/T polymorphism and the risk of type 2 diabetic retinopathy (T2DR) by a method of meta-analysis. Six online databases were queried to identify studies investigating the VEGF+936 C/T polymorphism that influenced T2DR up to August 2023. The statistical tool of the pooled data was adopted using Stata 15.0 software. The experimental group comprised patients with T2DR, while patients with type 2 diabetes mellitus without retinopathy were considered as the controls. The odds ratio (OR) was utilized as effect size. Eight eligible publications were identified in this review, including 1546 patients with T2DR. The combined results revealed that the VEGF+936 C/T polymorphism was significantly associated with the T2DR risk under the allelic (C/T: OR=0.54, p<0.001), the dominant (CC+CT/TT: OR=0.37, p<0.001), recessive (CC/CT+TT: OR=0.52, p=0.001), homozygous (CC/TT: OR=0.31, p<0.001), and heterozygous (CT/TT: OR=0.55, p=0.005) gene models. No significant correlation was observed regarding the VEGF+936 C/T polymorphism that contributed to the risk of proliferative diabetic retinopathy (PDR) versus non-PDR. In conclusion, the VEGF+936 C/T polymorphism significantly contributed to the T2DR risk. Specifically, at the VEGF+936 C/T locus, the presence of allele C and genotypes CC, CT, and CC+CT were found to be associated with a reduced risk of T2DR. [ABSTRACT FROM AUTHOR]

Voriconazole is the first‐line treatment for invasive aspergillosis. Its pharmacokinetics exhibit considerable inter‐ and intra‐individual variability. The purpose of this study was to investigate the effects of CYP2C19, CYP2C9, CYP3A4, and FMO3 genetic polymorphisms and sex on the pharmacokinetics of voriconazole in healthy Chinese adults receiving single‐dose and multiple‐dose voriconazole, to provide a reference for its clinical individualized treatment. A total of 123 healthy adults were enrolled in the study, with 108 individuals and 15 individuals in the single‐dose and multiple‐dose doses, respectively. Plasma voriconazole concentrations were measured using a validated LC‐MS/MS method, and pharmacokinetics parameters were calculated using the non‐compartmental method with WinNonlin 8.2. CYP2C19, CYP2C9, CYP3A4, and FMO3 single‐nucleotide polymorphisms were sequenced using the Illumina Hiseq X‐Ten platform. The results suggested that CYP2C19 genetic polymorphisms significantly affected the pharmacokinetics of voriconazole at single doses of 4, 6, and 8 mg/kg and multiple doses of voriconazole. CYP3A4 rs2242480 had a significant effect on AUC0‐∞ (area under the plasma concentration‐time curve from time 0 to infinity) and MRT (mean residence time) of voriconazole at a single dose of 4 mg/kg in CYP2C19 extensive metabolizer. Regardless of the CYP2C19 genotype, CYP2C9 rs1057910 and FMO3 rs2266780 were not associated with the pharmacokinetics of voriconazole at three single‐dose levels or multiple doses. No significant differences in most voriconazole pharmacokinetics parameters were noted between male and female participants after single and multiple dosing. For patients receiving voriconazole treatment, CYP2C19 genetic polymorphisms should be genotyped for its precision administration. In contrast, based on our study of healthy Chinese adults, it seems unnecessary to consider the effects of CYP2C9, CYP3A4, and FMO3 genetic polymorphisms on voriconazole pharmacokinetics. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a common autoimmune disease with a polymorphic clinical presentation involving multisystem damages with significant differences in prevalence and disease severity among different ethnic groups. Although genetic, hormonal, and environmental factors have been demonstrated to contribute a lot to SLE, the pathogenesis of SLE is still unknown. Numerous evidence revealed that gene variants within the type I interferons (IFN) signaling pathway performed the great genetic associations with autoimmune diseases including SLE. To date, through genome-wide association studies (GWAS), genetic association studies showed that more than 100 susceptibility genes have been linked to the pathogenesis of SLE, among which TYK2, STAT1, STAT4, and IRF5 are important molecules directly connected to the type I interferon signaling system. The review summarized the genetic associations and the detailed risk loci of STAT4 and IRF5 with Asian SLE patients, explored the genotype distributions associated with the main clinical manifestations of SLE, and sorted out the potential reasons for the differences in susceptibility in Asia and Europe. Moreover, the therapies targeting STAT4 and IRF5 were also evaluated in order to propose more personalized and targeted treatment plans in SLE. [ABSTRACT FROM AUTHOR]

To date, safe and effective strategies to prevent medically attended respiratory syncytial virus (RSV) illness across the infant population have been limited to passive immunoprophylaxis for those at highest risk. While active vaccination strategies are finally available to protect adults 60 years and older from serious RSV infection, safe and effective vaccines for use in children have yet to emerge. In contrast, passive immunization strategies designed to protect all infants against RSV has finally met with success, with 2 new strategies approved by the US Food and Drug Administration during the second half of 2023. The first RSV passive immunization strategy to gain licensure for use in all infants is an extended half-life monoclonal antibody directed against an antigenic binding site on the RSV-F prefusion protein, a conformation not known to exist until 2013. The second novel passive immunization strategy approved during 2023 that has the potential to protect much of the infant population from RSV during young infancy centers on boosting preexisting RSV immunity during pregnancy using a prefusion RSV-F vaccine. The resulting boosted humoral immune response to RSV in the mother becomes part of the transplacental antibody endowment that is actively transported across the placenta to provide protection to those babies born at or near term. This review describes how and why these advances came to fruition seemingly "all at once" and provides insight into other passive immunization approaches that remain under development. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a complex multifactorial disease. The association of knee OA risk with ACE gene rs4343 polymorphism, gene environment synergistic effect, and angiotensin II serum level has not been previously examined. Therefore, we investigate the ACE gene rs4343 polymorphism in knee OA, and its association with severity of knee OA, and angiotensin II serum level. Using a case–control design, we recruited 200 subjects (100 cases and 100 controls) and all were subjected to genotyping of rs4343 SNP by real-time polymerase chain reaction and assay of serum angiotensin II level by ELISA. G containing genotypes (AG and GG) and G allele frequencies of the ACE rs4343 polymorphism were significantly higher in the case group than that in the control group. There was significant association between ACE rs4343 genotypes and risk of knee OA under the following genetic inheritance models: GG vs. AA (P = 0.003), AA vs. GG/AG (P = 0.014), AG/AA vs. GG (P = 0.037), and G vs. A (P < 0.001). Stratified analyses showed ACE rs4343 polymorphism was evidently associated with a significantly increased risk of knee OA among those had BMI ≥ 25% (adjusted OR = 3.016; 95% CI 1.052–8.648; P = 0.040). Additionally, knee OA patients with GG genotype had greater knee specific WOMAC index, Kellgren score, and serum angiotensin II level than those with AA or GA genotypes. The investigated polymorphism in the ACE gene rs4343 may reflect the risk and severity of knee OA in the Egyptian population, particularly with the GG genotype. The interaction between ACE gene rs4343 polymorphism and obesity further increased the risk of knee OA. Moreover, the higher angiotensin II level may be involved in the pathogenesis of knee OA. [ABSTRACT FROM AUTHOR]

Background: Gallstone disease (GD) is common but remains asymptomatic in most cases. However, gallstones can lead to complications like choledocholithiasis or gallbladder cancer. In this study, we analyse the common genetic risk factor for GD, the p.D19H variant in the sterol transporter ABCG8, in Polish patients with gallstones and gallbladder cancer. Methods: Three adult cohorts were prospectively recruited: 65 patients with gallbladder cancer, 170 obese individuals scheduled for bariatric surgery and 72 patients who underwent endoscopic retrograde cholangiopancreatography due to recurrent choledocholithiasis. The control cohort consisted of 172 gallstone‐free adults. The ABCG8 p.D19H (rs11887534) polymorphism was genotyped using TaqMan assays. Results: The minor allele frequency (MAF) of the ABCG8 p.D19H polymorphism was significantly (p =.02) higher among cases with either gallstones or gallbladder cancer (MAF = 8.4%) as compared to controls (MAF = 4.0%). The highest frequency of the risk allele was detected in patients with gallbladder cancer (18.5%) and obese patients with GD (17.5%), followed by individuals with choledocholithiasis (13.9%). Notably, the p.19H variant was associated with an increased risk of developing gallbladder cancer (OR 2.76, 95% CI 1.16–6.54, p =.01) and an increased risk of GD in obese individuals scheduled for bariatric surgery (OR = 2.70, 95% CI 1.05–6.49, p =.03), but did not significantly affect the risk of choledocholithiasis. Conclusions: The ABCG8 p.D19H common risk variant increases the risk of developing gallbladder cancer in Central Europeans and enhances the risk of gallstones in the obese. Carriers of the p.D19H variant might benefit from personalized preventive strategies, particularly regarding gallbladder cancer. [ABSTRACT FROM AUTHOR]

Autoimmune neutropenia (AIN) in early childhood is characterized by chronic neutropenia and positivity for human neutrophil antibodies (HNA), resulting in the excessive destruction of neutrophils. The association between regulatory T cells (Tregs) and AIN has been described, and in this study, we investigated three Treg‐associated genes, IL‐2, IL‐10 and FOXP3. The frequencies of three single nucleotide polymorphisms (SNPs) in IL‐2 −330T>G (rs2069762), +114G>T (rs2069763) and IVS3‐116 A>G (rs2069772), four SNPs in IL‐10 −3575T>A (rs1800890), −1082G>A (rs1800896), −819 C>T (rs1800871) and −592 C>A (rs1800872) and three SNPs in FOXP3 –3499 A>G (rs3761547), −3279 C>A (rs3761548) and −924 A>G (rs2232365) were compared between 166 Danish AIN patients and 358 healthy controls. Disease association was observed for IL‐2 IVS3‐116 GG (p = 0.0081, OR = 0.35 [0.15–0.80]), IL‐10 −3575 TT (p = 0.0078, OR = 1.71 [1.16–2.54]) and IL‐10 −1082 AA (p = 0.014, OR = 1.76 [1.14–2.72]) in all patients and FOXP3 –924 (p = 0.0005, A OR = 0.41 [0.25–0.68] and G OR = 2.42 [1.46–4.01]) in male patients. None of the associations were linked to antibody specificity. Disease‐associated haplotypes were observed in IL‐2 and FOXP3. IL‐2 −330T/+114 T/IVS3‐116A was associated with anti‐FcγRIIIb‐positive patients (p = 0.012, OR = 2.07 [1.18–3.62]). FOXP3 –3499A/–3279C/−924A was associated with anti‐HNA‐1a‐positive male patients (p = 0.016, OR = 0.41 [0.20–0.83]), and ACG was associated with female patients, both in the combined group (p = 0.006, OR = NA) and the anti‐FcγRIIIb‐positive group (p = 0.002, OR = NA). We conclude that our findings reveal a correlation between SNP in Treg‐associated genes and AIN, indicating that AIN could be driven by dysfunction of immune homeostatic‐evolving Tregs. [ABSTRACT FROM AUTHOR]

In the study, it was aimed to determine the molecular characterization and genetic relationships of Mentha species obtained from different countries and regions at the molecular level and to ensure the sustainability of these species. For this purpose, ISSR marker technique, which is effective in detecting polymorphism and genetic variation within and between Mentha species, was used. In the study a total of 460 allelic bands were detected, and all bands were found to be 100% polymorphic. The maximum number of bands was produced by the ISSR7 primer (25), but the minimum number of bands was produced by the ISSR12 primer (13). The highest PIC (Polymorphism Information Content) value was detected in the ISSR3 primer (0.521) but the lowest PIC value was determined in the 903 primer (0.203). Molecular datas were analyzed using the NTSYSpc 2.02 software and it was determined that the mint species were divided into two main groups. In the results obtained, it was determined that there was no relationship between the genetic diversity and geographical origins, and the populations from different geographical regions were in the same clusters. In the study, it was concluded that there was a significant molecular diversity among the species, and that some Mentha clones, which are defined by morphological features and still remain taxonomically uncertain, were belong to which species at the molecular level. Therefore, it is insufficient to classify species with morphochemical, morphological and phenotypic characteristics. [ABSTRACT FROM AUTHOR]

Nonetheless the key roles of growth hormone (GH) and insulin growth factor-1 (IGF-1) genes in livestock growth traits (including body measurements), few studies deployed them in camels, unlike other livestock species (cattle, buffalo, sheep, and goat). So, this study was performed to investigate the genetic polymorphism of GH and IGF-1 markers, in Maghrabi camels by PCR-SSCP and DNA sequencing tools, with assessing the impacted live body measurements traits. In this study, 65 blood samples were collected from Maghrabi camel, and different body measurements were valued. Different genotypes of GH and IGF-1 genes were determined, via SSCP-PCR and sequencing tools. The results pointed out one genotype for the IGF-I gene, and three genotypes for the GH gene, with 23.21, 42.85, and 33.95 frequencies, of AA, AB, and BB genotypes, respectively. The sequence analysis showed specific single nucleotide polymorphisms (SNPs), for both A and B alleles. Those SNPs triggered alteration in some of the amino acids. Moreover, individuals of the BB genotype recorded the highest value in body weight, Neck length, Height at lumbar area, Anterior limb length, Neck circumference, and increased Body length associated with the AA genotype. Nevertheless, there were no significant differences, between the three genotypes, for the other body measurements. This study found that Maghrabi camels possess three genotypes of the GH gene and one genotype of the IGFI gene, and the BB genotype of the GH gene was associated with high performance of growth traits. Therefore, it is useful to use camel individuals, with the BB genotype of the GH gene, in camelid breeding programs, to improve live body measurement traits. [ABSTRACT FROM AUTHOR]