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Background: Many clinical variables might impact the pharmacokinetics of calcineurin inhibitors (CIs). Different alleles of cytochromes P450 (CYP)3A4/5 and drug transporter P-glycoprotein are the main variables. Other variables include relocated type, treatment duration after transplantation, age, sex, dietary consumption, medications used and renal or hepatic impairment. Tacrolimus and cyclosporine are two main CIs extensively used in organ transplantation. Both drugs are metabolized by CYP3A4 and CYP3A5 isoforms, and single-nucleotide polymorphisms in these genes have been displayed to influence CIs pharmacokinetics. Another important gene is the pregnane X receptor (PXR), which manages the statement of a variety of genes including CYP3A4 genes. PXR has a clinical significance in CIs metabolism. The liver is the essential site for CIs metabolism. A decreased clearance with a prolonged CIs half-life was occurred in patients with impaired liver compared with patients with normal liver function. The presence of different genetic and clinical factors that may affect calcineurin inhibitors trough levels will consequently affect their immunosuppressant effect after liver transplantation. Purpose: This study aims to determine the effect of different genetic polymorphisms in CYP3A4 1B rs2740574 and PXR A7635G rs6785049 and other clinical factors that may affect calcineurin inhibitors pharmacokinetics after liver transplantation. Results: The presence of T allele in CYP3A4 gene was associated with elevated DATLs with P values of 0.00, 0.00, 0.007 and 0.00 after tacrolimus doses 4, 30, 60 and 90, respectively. Regarding PXR gene, the presence of G allele was associated with elevated DATLs in cyclosporine. About 432 correlations were tested in both drugs. In CYP3A4 genotype CC, male sex was associated with elevated DATLs interpreted by strong positive correlations and statistically significant difference in all DATLs, except DATL 60 (P value 0.374). No strong association was found between low hemoglobin levels and DATLs in almost all the follow-up periods. There were many positive relations between increased total and direct bilirubin and increased DATLs. Conclusions: Studying the various genetics and clinical factors that may affect calcineurin inhibitors serum concentrations is very essential for successful treatment plans after organ transplantation. These different factors may interact with each other and these complicated interactions may complicate the patient's conditions post-transplantation. Considering all these complicated interactions is very crucial in monitoring treatment plans, especially in the presence of other comorbidities or chronic diseases. More studies with large number of patients should be conducted to explore more consequences of these interacting variables of treatment plans of these patients and all studied parameters in this study should be considered while monitoring patients after transplantation. [ABSTRACT FROM AUTHOR]

Background: A single nucleotide polymorphism (SNP) is a variation in the DNA sequence that results from the alteration of a single nucleotide in the genome. Atorvastatin is used to treat hypercholesterolemia. It belongs to a class of drugs called statins, which lower elevated levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). Research findings on the associations between the response to atorvastatin and genetic polymorphisms in CYP3A4 and CYP3A5 are inconclusive. The effects of CYP3A4*1B (rs2740574 C/T) and CYP3A5*3 (rs776746 T/C) on atorvastatin therapy have not been previously studied among Egyptians. Objective: This research aimed to investigate the effects of the genetic polymorphisms CYP3A4*1B and CYP3A5*3 on atorvastatin treatment in Egyptians. Methods: In this prospective cohort study, 100 subjects were genotyped for these SNPs. All participants were screened for serum lipid profiles, liver enzymes, total bilirubin (TB), and creatine kinase (CK) before and after 40 mg postatorvastatin therapy. Atorvastatin plasma levels were assessed posttreatment; atorvastatin pharmacokinetics were evaluated in five carriers of the CYP3A4*1B (T/T) and CYP3A5*3 (C/C) genotypes. Results: The allele frequencies of the CYP3A4*1B and CYP3A5*3 SNPs were 86% and 83%, respectively. The CYP3A4*1B (T/T) and CYP3A5*3 (C/C) genotypes significantly improved the serum triglyceride (TG) level (P < 0.05) and elevated the TB level (P < 0.001). Atorvastatin plasma levels were greater in CYP3A4*1B (T/T) (P < 0.05) and CYP3A5*3 (C/C) (P < 0.001) genotype carriers. Both SNPs significantly affected the pharmacokinetics of atorvastatin compared with those of Egyptian volunteers and various ethnic populations. Conclusions: The CYP3A4*1B and CYP3A5*3 variants were prevalent in the study participants and could impact the effectiveness and safety of atorvastatin therapy. The mutant genotype of the CYP3A4*1B SNP and the CYP3A5*3 SNP led to high atorvastatin levels. Both variants had a notable effect on the pharmacokinetics of atorvastatin among Egyptians compared with healthy Egyptians and volunteers from other ethnic populations. Overall, clinicians can learn more about the impact of both variants in response to atorvastatin. [ABSTRACT FROM AUTHOR]

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

Beyond the essential role of p27Kip1 and cyclin D2 in cell cycle progression, they are also shown to confer an anti-apoptotic function in peripheral blood (PB) lymphocytes. Although the aberrant longevity and expression of p27Kip1 and cyclin D2 in leukemic cells is well documented, the exact mechanisms responsible for this phenomenon have yet to be elucidated. This study was undertaken to determine the associations between polymorphisms in the CDKN1B and CCND2 genes (encoding p27Kip1 and cyclin D2, respectively) and susceptibility to chronic lymphocytic leukemia (CLL), as well as their influence on the expression of both cell cycle regulators in PB leukemic B cells and non-malignant T cells from untreated CLL patients divided according to the genetic determinants studied. Three CDKN1B single-nucleotide polymorphisms (SNPs), rs36228499, rs34330, and rs2066827, and three CCND2 SNPs, rs3217933, rs3217901, and rs3217810, were genotyped using a real-time PCR system. The expression of p27Kip1 and cyclin D2 proteins in both leukemic B cells and non-malignant T cells was determined using flow cytometry. We found that the rs36228499A and rs34330T alleles in CDKN1B and the rs3217810T allele in the CCND2 gene were more frequent in patients and were associated with increased CLL risk. Moreover, we observed that patients possessing the CCND2rs3217901G allele had lower susceptibility to CLL (most pronounced in the AG genotype). We also noticed that the presence of the CDKN1Brs36228499CC, CDKN1Brs34330CC, CDKN1Brs2066827TT, and CCND2rs3217901AG genotypes shortened the time to CLL progression. Statistically significant functional relationships were limited to T cells and assigned to CDKN1B polymorphic variants; carriers of the polymorphisms rs34330CC and rs36228499CC (determining the aggressive course of CLL) expressed a decrease in p27Kip1 and cyclin D2 levels, respectively. We indicate for the first time that genetic variants at the CDKN1B and CCND2 loci may be considered as a potentially low-penetrating risk factor for CLL and determining the clinical outcome. [ABSTRACT FROM AUTHOR]

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

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

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

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

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

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

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

Objective To analyze the relationship of miRNA-146a gene polymorphisms and ischemic post- stroke depression (PSD). Methods The SNP rs2910164 in the miRNA-146a gene in 200 ischemic PSD patients (case group) and 200 ischemic non-PSD patients (control group) was analyzed using the SNaPshot technique. The relative expression levels of miRNA-146a in the peripheral blood of two groups were determined. Results The case group showed significantly different allele and genotype frequencies of the SNP rs2910164 as compared with the control group (G vs. C : P = 0.003 ; GG + CG vs. CC : P = 0.012). Meanwhile, the case group presented a significantly lower level of miRNA-146a relative expression (P < 0.05). Within the control group, additionally, the subgroup of GG + CG genotypes demonstrated a significantly lower level of miRNA-146a relative expression compared with the subgroup of CC genotypes (P < 0.05). Conclusion SNP rs2910164 in the miRNA-146a is associated with the susceptibility to ischemic PSD, and G allele may play a role in the ischemic PSD. [ABSTRACT FROM AUTHOR]

Background: To investigate the association of vitamin D receptor (VDR) gene polymorphism with caries risk in children(< 18 years). Methods: The electronic databases PubMed, Cochrane, EMBASE, Web of Science, CNKI, Cqvip, and Wanfang were searched for observational studies on the relationship between VDR single nucleotide polymorphism(SNP) and caries, including cohort, case–control, and cross-sectional studies. Quality assessment of selected studies was conducted using the Newcastle Ottawa scale. Odds ratios (OR) with 95% confidence intervals (CI) values for associations of individual VDR SNP with dental caries were calculated based on four genetic models: allelic, recessive, dominant, and over-dominant. Results: Of 79 studies considered, 10 (nine case–control and one cross-sectional) were selected for analysis; the studies involved seven VDR SNPs: ApaI(rs7975232),BsmI(rs1544410),FokI(rs2228570),TaqI(rs731236), TaqI/BglI(rs739837), FokI(rs10735810) and Cdx-2(rs11568820). Alleles C and T of FokI(rs10735810) were significantly differently distributed in the caries and caries-free groups (OR = 1.33, 95% CI: 1.30–2.30, P = 0.03), with CC + CT genotypes at this locus associated with greater risk of developing caries than the TT genotype (OR = 1.87, 95%CI: 1.15–3.04, P = 0.01). Further, TT + CC genotype at TaqI(rs731236) was associated with a 1.33-fold higher risk of caries development than the TC genotype (OR = 1.33, 95%CI: 1.06–1.67, P = 0.02). On subgroup analysis, the association between TaqI(rs731236) and caries risk was affected by dentition type, and ethnicity (permanent dentition: OR = 1.48, 95%CI: 1.07–2.03, P = 0.02; Asian: OR = 1.38, 95%CI: 1.02–1.87, P = 0.03;). Genotype distributions at BsmI(rs1544410), TaqI/BglI(rs739837), FokI(rs2228570), and ApaI(rs7975232) did not differ significantly between the caries and caries-free groups. Conclusions: Caries risk could be associated with TaqI(rs731236) and FokI(rs10735810) genotypes, and TaqI(rs731236) may be a risk factor for permanent teeth caries among Asian people. [ABSTRACT FROM AUTHOR]

Background and Aim: Milk physicochemical properties play essential role in the milk processing industry, which are moderately to highly affected by genetic factors. This study aimed to evaluate the association between single nucleotide polymorphisms in POU class 1 homeobox 1 (POU1F1) and the physicochemical properties of milk in high-producing Holstein Friesian (HF) cows. Materials and Methods: A total of 149 high-producing dairy cows from PT Ultra Peternakan Bandung Selatan was included in this study. The physicochemical properties of milk, including density, freezing point, pH, lactose, solid non-fat, protein, and ash content, were determined. Moreover, three polymorphisms within the exon regions of POU1F1 (c.195G>A, c.300G>T, and c.828G>A) were analyzed using polymerase chain reaction-restriction fragment length polymorphism. The association between these polymorphisms and the physicochemical properties of milk was determined using a mixed-effects model analysis, in which the lactation period was used as a covariate. Results: This study found that two polymorphisms, c.195G>A and c.828G>A, significantly affected the pH of fresh milk. Cows with both the GG genotypes c.195G>A and c.828G>A had lower milk pH values than those with the other genotypes. In addition, a non-significant effect of POU1F1 was observed on the other physicochemical properties of milk. Conclusion: Two POU1F1 polymorphisms determined the pH of fresh milk in the Indonesian HF population. These are potential marker candidates for milk pH that directly affect the development of dairy products in the milk processing industry. [ABSTRACT FROM AUTHOR]

Introduction: The North-eastern Region of India has been a rich reservoir of haemoglobinopathies and thalassaemias. Genetic modifiers, commonly known as ameliorating factors, like co-inheritance of α-thalassaemia, excess α genes, the presence of the XmnI Gγ polymorphism and BCL11 Single Nucleotide Polymorphisms (SNPs), influence the reduction of the severity of Beta-thalassaemia. Early genetic diagnosis can aid in predicting a better prognosis and lower morbidity in thalassaemic children. Aim: To find out the XmnI polymorphism among thalassaemic children admitted to the Paediatric Department for regular blood transfusions and to assess the relationship between XmnI polymorphism, disease severity and foetal haemoglobin levels. Materials and Methods: This hospital-based cross-sectional study was done from June 2020 to May 2021 in the Department of Paediatrics and Anatomy at Assam Medical College and Hospital, Dibrugarh, Assam, India. A total of 96 thalassaemic children presenting to the thalassaemia daycare centre of the Paediatrics Department for repeated blood transfusions were included. Data collected from history and examination findings were recorded and the presence of XmnI polymorphism in their blood was tested using the Polymerase Chain Reaction-Restriction Fragment-length Polymorphism (PCR-RFLP) method. The association of XmnI polymorphism with disease severity and foetal haemoglobin levels was analysed using the Chi-square test, with a p-value of <0.05 considered significant. Results: The mean age of the children was 10.1±4.4 years (range: 2 to 18 years), with a male-to-female ratio of 0.95:1. Among the participants, 59 (61.46%) had Haemoglobin (Hb) E-ß thalassaemia and 37 (38.54%) had ß thalassaemia homozygous type. A total of 47 (48.96%) children exhibited the presence of XmnI polymorphism, of which 16 (34%) had ß-thalassaemia homozygous and 31 (66%) had Hb E-ß thalassaemia. A significant association was found between this polymorphism and disease severity (p<0.001), but no significant association was observed with HbF levels (p=0.089). XmnI polymorphism was associated with hepatomegaly and stunting. Conclusion: The present study demonstrated that the presence of XmnI polymorphism in thalassaemic children was associated with decreased disease severity, as these children presented at a later age and required fewer blood transfusions than those without this polymorphism. No association was found between XmnI polymorphism and HbF levels in the present study. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a major public health problem worldwide, currently ranking third in cancer incidence and second in mortality. Multiple genes and environmental factors have been involved in the complex and multifactorial process of CRC carcinogenesis. VDR is an intracellular hormone receptor expressed in both normal epithelial and cancer colon cells at various levels. Several VDR gene polymorphisms, including FokI and BsmI, have been evaluated for their possible association with CRC susceptibility. The aim of our study was to investigate these two SNPs for the first time in Romanian CRC patients. FokI (rs228570 C>T) and BsmI (rs1544410 A>G) were genotyped by real-time polymerase chain reaction (RT-PCR) in 384-well plates using specific TaqMan predesigned probes on a ViiA™ 7 RT-PCR System. A total of 441 subjects (166 CRC patients and 275 healthy controls) were included. No statistically significant difference was observed between CRC patients and controls when we compared the wild-type genotype with heterozygous and mutant genotypes for both FokI (OR 0.85, 95% CI: 0.56–1.28; OR 0.95, 95% CI: 0.51–1.79, respectively) and BsmI (OR 0.97, 95% CI: 0.63–1.49; OR 1.10, 95% CI: 0.65–1.87, respectively) or in the dominant and recessive models. Also, we compared allele frequencies, and no correlation was found. Moreover, the association between these SNPs and the tumor site, TNM stage, and histological type was examined separately, and there was no statistically significant difference. In conclusion, our study did not show any association between FokI and BsmI SNPs and CRC susceptibility in a Romanian population. Further studies including a larger number of samples are needed to improve our knowledge regarding the influence of VDR polymorphism on CRC susceptibility. [ABSTRACT FROM AUTHOR]

The article presents an analysis of the gynogenesis (Zm_Pla1, Zm_CenH3, Zm_Dmp7) genes originated from haploid-inducing (ZMS-8, ZMS-P) and control (KM, GPL-1) maize lines of Saratov breeding. By sequencing and subsequent multiple alignment of the target gene transcripts of the studied maize lines and the reference B73 line, the presence of single nucleotide polymorphism (SNP), deletions, and insertions were determined, phylogenetic trees for the studied genes were constructed. The presence of a 4-nucleotide insertion (4NI) in the Zm_Pla1 gene originated from the Stock 6 ancestral line has been established in haploid-inducing (ZMS-8 and ZMS-P) maize lines, as well as 15 identical SNP. But the parthenogenetic AT-1, AT-3 and AT-4 maize lines, which also have Stock 6 as ancestral line, lack of 4NI in the Zm_Pla1 gene. Phylogenetic analysis of the Zm_Pla1 gene confirmed the relationship of the haploid-inducing Stock 6, ZMS-P, and ZMS-8 maize lines. The Zm_Dmp7 gene recorded the presence of 5 SNP in the ZMS-8 line and 3 SNP in the ZMS-P and KM maize lines. One of the SNP (at position 131 from the start codon) in the Zm_Dmp7 gene is the cause of the increased haploid-inducing ability of the CAU5, but not the ZMS-P maize line. In addition, a 3-nucleotide deletion was found in the Zm_Dmp7 gene in the ZMS-P line and a 9-nucleotide deletion in the KM maize line. [ABSTRACT FROM AUTHOR]

Objective: To explore the genetic susceptibility of MIF and MMPs family gene polymorphisms to ankylosing spondylitis (AS), as well as the correlation of gene-gene, gene-environment interactions in the pathogenesis of AS, and to find high risk factors of AS and screening of high-risk groups of AS. Methods: A total of 180 AS patients and 345 controls were included in this casecontrol study. Selected the tag SNPs of MIF and MMPs family genes (MIF rs2070767, MIF rs1007888, MMP1 rs498186, MMP2 rs243866, MMP3 rs591058, MMP8 rs11225395), then DNA was extracted and genotyped, and the relationship between genotype, allele distribution frequency, genetic model and the incidence of AS and the risk factors were further analyzed. Generalized multi-factor dimensionality reduction method was used to analyze the correlation of the interaction between target genes and between genes and the environment and AS. The functional enrichment analysis and immune correlation analysis of MIF and MMPs were carried out. Results: The genotype distribution frequency of the smallest alleles of MIF rs1007888, MMP1 rs498186, MMP8 rs11225395 were higher risks in AS group than in control group (P<0.05). GG genotype of MIFrs1007888, GG genotype of MMP1 rs498186, CT/TT genotype of MMP3 rs591058, and TT genotype of MMP8 rs11225395 were related to the risk of AS. Gene-gene interaction analysis found that MMP3 rs591058 and MMP8 rs11225395 interaction models were the best models. Gene-environment interaction analysis found that MIF rs2070767, MIF rs1007888, MMP1 rs498186, MMP2 rs243866, MMP3 rs591058, MMP8 rs11225395, smoking, drinking, and obesity interaction models were the best models. MIF and MMPs related genes were enriched in matrix metalloproteinases, macrophage migration pathway and immune system regulation. Expression levels of MMPs were positively correlated with immune infiltration. Conclusion: The single nucleotide polymorphisms of MIF and MMPs are related to the susceptibility to AS, and there is an interaction between MIF and MMPs genes and the environment, which causes as through multiple biological processes, and may affect the process of as through immune infiltration. [ABSTRACT FROM AUTHOR]

Background: Recipient's VEGF‐A polymorphisms have been reported to be associated with the risk of acute allograft rejection. However, an association of the donor's VEGF‐A gene polymorphism with rejection remained unelucidated till now. Methods: In this study, VEGF‐A gene SNPs at nine loci were analyzed in 160 kidney donors and recipients with rejection (rejectors, n = 80) and without rejection (non‐rejectors, n = 80). Blood VEGF‐A mRNA, plasma VEGF level, and intragraft VEGF expression were also analyzed by RT‐PCR, ELISA, and immunohistochemistry, respectively. Results: On comparing between the donor and rejectors, the polymorphic genotypes of VEGF –634 C>G [GG genotype, p < 0.0001; OR (95% CI) = 17.74 (5.16–60.96)]; VEGF –1154 G>A [AG genotype, p < 0.0001, OR (95% CI) = 16.07 (3.68–70.15)]; VEGF +936 C>T [CT genotype, p < 0.0001, OR (95% CI) = 178.64 (23.28–1370.9), and TT genotype, p < 0.0001; OR (95% CI) = 3149 (278.91–35 553)]; VEGF –1455 T>C [CC genotype, p value = 0.0464, OR (95% CI) = 3.13 (1.07–9.10)]; VEGF –2578 C>A [CA genotype, p = 0.0426, OR (95% CI) = 4.62 (1.03–20.59), and AA genotype, p value < 0.0001, OR (95% CI) = 21.89 (4.94–97.04)]; VEGF –2549 18 bp Insertion/Deletion [ID genotype, p value < 0.0001, OR (95% CI) = 27.27 (3.61–205.73) and DD genotype, p value < 0.0001, OR (95% CI) = 25.18 (3.30–191.89) were significantly associated with acute rejection risk. On comparing rejectors versus non‐rejectors, GA genotype of VEGF –1190 G>A and TC genotype of VEGF –1455 T>C were associated with the risk of rejection. On comparing donor VEGF between rejectors and non‐rejectors, CG genotype of VEGF –634 C>G, AG of VEGF –1154 G>A; GA of VEGF –1190 G>A were associated with rejection. The blood VEGF‐A mRNA and plasma VEGF levels were higher in the rejectors group compared to non‐rejectors. Conclusions: Besides the recipient's VEGF SNPS, the donor's VEGF SNPs are also associated with the risk of acute rejection and may be closely monitored in evaluation to determine the risk of rejection. [ABSTRACT FROM AUTHOR]

Growth factor receptor-bound protein 2 (GRB2) is a negative regulator of insulin signaling and a positive regulator of angiogenesis. Its expression is increased in a mouse model of retinal neovascularization and in patients with type 2 diabetes mellitus (T2DM). This case–control study aimed to investigate the association between the rs9896052 polymorphism (A>C) upstream of GRB2 and proliferative diabetic retinopathy (PDR) in patients with T2DM from Southern Brazil, taking into consideration self-reported skin color (white or non-white) and the known duration of diabetes (<10 years or ≥10 years). Genotypes were determined by real-time PCR in 838 patients with T2DM (284 cases with PDR and 554 controls without DR). In the total study group and in the analysis stratified by skin color, the genotype and allele frequencies were similar between cases and controls. However, among patients with less than 10 years of diabetes, the C allele was more frequent in cases than in controls (63.3% versus 51.8%, p = 0.032), and the CC genotype was independently associated with an increased risk of PDR (adjusted OR = 2.82, 95% CI 1.17–6.75). In conclusion, our findings support the hypothesis that the rs9896052 polymorphism near GRB2 is associated with PDR in Brazilian patients with T2DM. [ABSTRACT FROM AUTHOR]

Simple Summary: Our study aimed to understand why some people with lung adenocarcinoma, a type of lung cancer, survive longer than others, even when their conditions seem similar. By studying the DNA of 1464 patients, we found six specific genetic differences that appear to affect survival. These differences are located in parts of the DNA that do not directly make proteins but might control how certain genes are turned on or off. The goal is to use this information to predict which patients might have better outcomes and to develop more personalized treatment options. Further research is needed to confirm these results and to understand the underlying biological mechanisms, but our findings could eventually improve how we treat lung cancer and understand its outcomes better. Background/Objectives: Lung cancer remains a global health concern, with substantial variation in patient survival. Despite advances in detection and treatment, the genetic basis for the divergent outcomes is not understood. We investigated germline polymorphisms that modulate overall survival in 1464 surgically resected lung adenocarcinoma patients. Methods: A multivariable Cox proportional hazard model was used to assess the association of more than seven million polymorphisms with overall survival at the 60-month follow-up, considering age, sex, pathological stage, decade of surgery and principal components as covariates. Genes in which variants were identified were studied in silico to investigate functional roles. Results: Six germline variants passed the genome-wide significance threshold. These single nucleotide polymorphisms were mapped to non-coding (intronic) regions on chromosomes 2, 3, and 5. The minor alleles of rs13000315, rs151212827, and rs190923216 (chr. 2, 3 and 5, respectively) were found to be independent negative prognostic factors. All six variants have been reported to regulate the expression of nine genes, seven of which are protein-coding, in different tissues. Survival-associated variants on chromosomes 2 and 3 were already reported to regulate the expression of NT5DC2 and NAGK, with high expression associated with the minor alleles. High NT5DC2 and NAGK expression in lung adenocarcinoma tissue was already shown to correlate with poor overall survival. Conclusions: This study highlights a potential regulatory role of the identified polymorphisms in influencing outcome and suggests a mechanistic link between these variants, gene expression regulation, and lung adenocarcinoma prognosis. Validation and functional studies are warranted to elucidate the mechanisms underlying these associations. [ABSTRACT FROM AUTHOR]

The Eurasian wild boar (Sus scrofa), having faced a population size reduction during the nineteenth and early twentieth centuries, is now experiencing a remarkable population recovery, not only confined to natural habitats alone, but also thriving in human-dominated environments. Previously, studies on wild boars predominantly relied on the analysis of supposedly neutral molecular markers (e.g., microsatellites and single nucleotide polymorphisms). In this study, a next-generation sequencing approach was used to examine the adaptive variation at the second exon of the SLA-DRB1 locus in 116 wild boars from the western Balkans. A total of 17 functional SLA-DRB1 alleles were detected which translated into 14 different amino-acid sequences. In 12 individuals, we observed alleles at duplicated SLA-DRB1 loci. Spatial analysis revealed the presence of three genetic clusters, albeit with relatively low overall differentiation (an average FST value of 0.012). Positive selection was detected on only one codon, as indicated by multiple tests, while the presence of shared alleles among related species suggested signals of trans-species polymorphism. Our results indicate the high MHC diversity at the SLA-DRB1 locus in wild boars from the Balkan Peninsula, shaped by a complex interplay of several non-exclusive mechanisms, including balancing selection, recombination, and gene duplications. [ABSTRACT FROM AUTHOR]

Beclin 1 protein encoded by the BECN1 gene plays a critical role in the autophagy pathway which is utilized by the Hepatitis B virus (HBV) for its replication. HBV is known for the subversion of the host's autophagy process for its multiplication. The aim of this study was to determine the role of BECN1 intronic variants in HBV susceptibility. Intronic region variant rs9890617 was analyzed using Human splicing finder v3.1 and was found to alter splicing signals. A total of 712 individuals (494 HBV infected and 218 healthy controls) were recruited in the study and genotyped by applying Polymerase Chain Reaction–Restriction Fragment Length Polymorphism (PCR–RFLP). Statistical analysis revealed that the mutant allele T of rs9890617 was significantly associated with the overall disease risk in the allelic model (OR 1.41; 95%CI 1.00–1.99, p = 0.04). On stratifying the data based on the different stages of HBV infection, the mutant genotype showed a significant association with the chronic group in allelic (OR 1.62; 95%CI 1.11–2.39, p = 0.01), dominant (OR 1.64; 95%CI 1.07–2.52, p = 0.02), and co-dominant (OR 1.55; 95%CI 1.00–2.40, p = 0.04) models. Overall, this is the first study regarding beclin 1 variant rs9890617 and we found a significant association of the mutant T allele with the genetic predisposition to HBV infection. [ABSTRACT FROM AUTHOR]

Systemic Lupus Erythematosus (SLE) is an autoimmune disorder characterized by autoantibody production and organ involvement. The role of toll-like receptor-7 in SLE is well established. Although genetic variations in the TLR-7 gene have been associated with an increased risk of developing SLE, the findings are not consistent. We performed a meta-analysis of previously published articles on four important single nucleotide polymorphisms in the TLR-7 gene (rs3853839, rs179008, rs179019, and rs179010) to reach a valid conclusion. Various literature databases, including PubMed, Science Direct, and Scopus, were scoured for eligible reports until May 10, 2023. GPower software v.3 was used to assess the power of individual reports included in the meta-analysis. Comprehensive Meta-analysis v3 software was used to perform all statistics. The publication biases in each genetic comparison model were investigated using funnel plots and Egger's regression test. To test heterogeneity, Cochrane Q statistics, probability value and I2 were used. Considering the predefined inclusion and exclusion criteria, the current study included a total of 10 eligible studies that included 15,472 SLE cases and 16,721 healthy controls. The meta-analysis revealed a significant association between TLR7 polymorphisms (rs179019 and rs179010) and susceptibility to SLE development. Other TLR7 polymorphisms (rs3853839 and rs179008), on the other hand, showed no significant association. Furthermore, the trial sequential analysis identified the need for additional case control studies for TLR-7 polymorphisms (rs3853839, rs179008, and rs179019) other than the rs179010 polymorphism. TLR7 variants for rs179010 and rs179019 are risk factor for the development of SLE. Further investigations are required to reach a valid conclusion. [ABSTRACT FROM AUTHOR]

The TMPRSS2 protease plays a key role in the entry of the SARS-CoV-2 into cells. The TMPRSS2 gene is highly polymorphic in humans, and some polymorphisms may affect the susceptibility to COVID-19 or disease severity. rs75603675 (c.23G > T) is a missense variant that causes the replacement of glycine with valine at position 8 (p.G8V) in the TMPRSS2 isoform 1. According to GnomAD v4.0.0 database, the allele frequency of the rs75603675 on a global scale is 38.10 %, and range from 0.92 % in East Asian to 40.77 % in non-Finnish European (NFE) population. We analyzed the occurrence of the rs75603675 in two cohorts of patients, the first with severe/critical COVID-19 enrolled in a French hospital (42 patients), and the second with predominantly asymptomatic/pauci-symptomatic/mild COVID-19 enrolled in an Italian hospital (69 patients). We found that the TMPRSS2 -c.23T minor allele frequency was similar in the two cohorts, 46.43 % and 46.38 %, respectively, and higher than the frequency in the NFE population (40.77 %). Chi-square test provided significant results (p < 0.05) when the genotype data (TMPRSS2 -c.23T/c.23T homozygotes + TMPRSS2 -c.23G/c.23T heterozygotes vs. TMPRSS2 -c.23G/c.23G homozygotes) of the two patient groups were pooled and compared to the expected data for the NFE population, suggesting a possible pathogenetic mechanism of the p.G8V substitution. We explored the possible effects of the p.G8V substitution and found that the N-terminal region of the TMPRSS2 isoform 1 contains a signal for clathrin/AP-2-dependent endocytosis. In silico analysis predicted that the p.G8V substitution may increase the accessibility to the endocytic signal, which could help SARS-CoV-2 enter cells. • Polymorphism rs75603675 is a missense variant that causes the replacement of glycine with valine at position 8 in TMPRSS2 • Minor allele of rs75603675 is associated with increased susceptibility to COVID-19 in a retrospective cohort analysis. • G8V substitution affects the stability of the N-terminal region of the TMPRSS2 as revealed by molecular dynamic simulation. • In silico analysis shows that an endocytic signal may be more exposed in TMPRSS2-p.8V variant, helping the virus enter cells. [ABSTRACT FROM AUTHOR]

The aim of this study was to examine particular single-nucleotide polymorphisms (IL-1A-889 C/T — rs1800587, IL-1B +3953 C/T — rs 1143634) of interleukins 1A and 1B in the development and prognosis of medication-related osteonecrosis of the jaw. DentiGen Parodontitis Tests were applied for collecting samples. This test is suitable for sampling oral mucosa cells in order to detect interleukins 1A and 1B single nucleotide polymorphisms (IL-1A−889, IL-1B+3953). Genetic samples were evaluated in the Istenhegyi Genediagnostic Center using the DNA-hybridization method. Genetic samples were collected in the patient group and the control group. The role of gene polymorphisms in the development of the disease was investigated by comparing the genetic results for the patient and control groups. The investigation of gene polymorphisms in disease prognosis is based on stage improvement, recovery, and relapses following treatment. In total, 91 patients with MRONJ and 59 healthy controls were included in the study. 51 patients in the patient group and 37 controls had unfavorable allelic variants. No association (Mp = 1.42, SDp = 0.496, Mc = 1.35, SDc = 0.482, p = 0.52) was found between unfavorable polymorphisms and the development of the MRONJ. In the patient group, surgical therapy was required in 79 cases. Stage improvement was detected in 78 cases, recovery in 67 cases, and relapse in 33 cases. No stage improvement was found in one case, recovery in nine cases, or relapse in 34 cases. Of the 79 patients requiring surgical therapy, 49 had unfavorable allelic variants. No connection was found between the polymorphisms examined and stage improvement (Mp = 1.37, SDp = 0.486, Mnp = 2, SDnp = –, p = 0.800) or recovery (Mp = 1.39, SDp = 0.491, Mnp = 1.44, SDnp = 0.527, p = 0.990). However, a significant association (Mp = 1.21, SDp = 0.415, Mnp = 1.58, SDnp = 0.502, p < 0.001) was found between relapses and the presence of unfavorable allelic variants. Within the possible limitations of this study, it can be assumed that the analysis of certain single-nucleotide polymorphisms of interleukin-1 may have the potential to help define the risk stratification of MRONJ after surgical therapy. [ABSTRACT FROM AUTHOR]

Background: Gliomas are neoplasms of the central nervous system that originate in glial cells. The genetic characteristics of this type of neoplasm are the loss of function of tumor suppressor genes such as TP53 and somatic mutations in genes such as IDH1/2. Additionally, in clinical cases, de novo single nucleotide polymorphisms (SNP) are reported, of which their pathogenicity and their effects on the function and stability of the protein are known. Methodology: Non-synonymous SNPs were analyzed for their structural and functional effect on proteins using a set of bioinformatics tools such as SIFT, PolyPhen-2, PhD-SNP, I-Mutant 3.0, MUpro, and mutation3D. A structural comparison between normal and mutated residues for disease-associated coding SNPs was performed using TM-aling and the SWISS MODEL. Results: A total of 13 SNPs were obtained for the TP53 gene, 1 SNP for IDH1, and 1 for IDH2, which would be functionally detrimental and associated with disease. Additionally, these changes compromise the structure and function of the protein; the A161S SNP for TP53 that has not been reported in any databases was classified as detrimental. Conclusions: All non-synonymous SNPs reported for TP53 were in the region of the deoxyribonucleic acid (DNA) binding domain and had a great impact on the function and stability of the protein. In addition, the two polymorphisms detected in IDH1 and IDH2 genes compromise the structure and activity of the protein. Both genes are related to the development of high-grade gliomas. All the data obtained in this study must be validated through experimental approaches. [ABSTRACT FROM AUTHOR]

One of the causes of coronary heart disease (CHD) is genetic factors. In this study, we explored the relationship between CYP2D7 and TCF20 gene polymorphisms and the risk of CHD in the Han Chinese population. Three single nucleotide polymorphisms (CYP2D7 rs1800754, CYP2D7 rs2743461, and TCF20 rs760648) were selected and genotyped from 490 cases and 480 controls. The odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association between CYP2D7 and TCF20 polymorphisms and the risk of CHD. The association between clinical indicators and polymorphisms was analyzed using one-way ANOVA and Tukey's HSD. The SNP-SNP interactions were obtained by performing multifactor dimensionality reduction (MDR). CYP2D7 rs1800754 and rs2743461 were closely associated with increased risk of CHD (alleles: p = 0.014, p = 0.031). Stratified analysis showed that CYP2D7 rs1800754 and rs2743461 were associated with an increased risk of CHD in men, age > 60 years, BMI ≥ 24, and smoking. Rs1800754 is also associated with an increased risk of CHD associated with alcohol consumption. In addition, TCF20 rs760648 was associated with a reduced risk of CHD in patients aged ≤ 60 years and with CALs. A significant association was found between CYP2D7 rs1800754 and rs2743461 genotypes and levels of UREA, Cr, and LDL-C; TCF20 rs760648 genotypes and levels of RBC. The MDR analysis showed that the three-locus interaction model was the best in the multi-locus model. In conclusion, CYP2D7 rs1800754 and rs2743461 polymorphisms were associated with CHD risk. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the utility of 24 single nucleotide polymorphism (SNP) loci associated with iris color and hair color in phenotypic identification of the Han Chinese population in Fujian Province. The selected SNPs, known for their strong correlation with specific human phenotypic features, provide valuable reference data for developing a molecular phenotypic identification system. Methods: A multiplex genotyping assay system was established with primers for the 24 SNPs linked to iris color and hair color synthesized based on existing literature. In total, 235 unrelated individuals of Han Chinese ethnicity in Fujian Province were included in this study. PowerStats v12 was employed to calculate forensic parameters associated with the 24 SNP loci, including gene frequencies, genotype frequencies, minor allele frequencies, discrimination power (DP), polymorphism information content (PIC), and observed heterozygosity (Ho). Hardy- Weinberg equilibrium tests were conducted for each locus. The SNP genotyping results were uploaded to the HIrisPlex model (https://HIrisPlex.erasmusmc.nl/) to predict iris and hair colors, and the inferred results were compared with manually assessed images. The accuracy of pigment phenotype inference was evaluated by using ROC curves in SPSS 26.0 software. Results: The accuracy rates of inferring brown iris and black hair phenotypes were 99.6% and 99.5%. The area under the curve (AUC) values were 0.923 and 0.980, respectively. Conclusions: The 24 SNP loci demonstrated high accuracy in inferring iris color and hair color; it seems to be a useful tool for forensic phenotypic identification and anthropological or evolutionary applications. Establishment of suitable pigment classification criteria and optimized prediction models is based on revealing more phenotypic genetic markers. [ABSTRACT FROM AUTHOR]

A diverse collection of congenital disorders influencing chromosomal, gonadal, or anatomical sex traits is known as disorders of sex development (DSD). These conditions encompass a wide spectrum of phenotypes, including hypospadias, ambiguous genitalia, and complete sex reversal. Human gonadal development relies on complex genetic and hormonal interactions, with disruptions often leading to DSD. This case-sectional study included 110 participants recruited from a pediatric surgery department. Blood samples were utilized to isolate genomic DNA, followed by genotyping of the MTHFR gene polymorphism (rs1801133) through real-time PCR. Subsequently, a statistical analysis was conducted to assess and compare genotype frequencies across both case and control groups. Genotype distribution analysis revealed no significant difference in MTHFR (C677T) polymorphism frequencies between case and control groups. Allelic frequencies showed a slightly higher prevalence of the C allele in controls compared to cases. Analysis under dominant and recessive genetic models indicated a potential association between MTHFR polymorphism and DSD, particularly under the dominant model. This study contributes to understanding the genetic underpinnings of DSD, suggesting a possible association between MTHFR polymorphism and DSD susceptibility, especially under the dominant genetic model. Additional research involving larger groups of subjects is required to authenticate these discoveries and clarify MTHFR's exact contribution in DSD's pathogenesis. An improved understanding of these genetic factors could enhance diagnostic accuracy and inform personalised treatment strategies for individuals with DSD. [ABSTRACT FROM AUTHOR]

Background: A possible role of vitamin D epimers and metabolites in the measurement and response to treatment of vitamin D has been reported recently. Furthermore, the influence of underlying vitamin D receptor (VDR) genetic polymorphisms which have been linked to diseases such as obesity remains unclear. We therefore aimed to examine the influence of vitamin D3 and calcium supplements on vitamin D epimer and metabolite concentrations in subjects with and those without vitamin D receptor (VDR) gene polymorphisms. Methods: A total of 277 participants who were part of a randomized intervention trial of vitamin D3 and calcium or a placebo for 6 months had clinical and anthropometric assessments. Blood samples were taken for measurements of vitamin D, epimers and metabolites of vitamin D, four vitamin D receptor gene polymorphism SNPs, namely, BsmI, FokI, TaqI, and ApaI, metabolic and inflammatory markers, and related biochemical variables. Repeated-measures analysis of variance was used to assess the between-group difference in cumulative changes in vitamin D epimers and metabolites at 6 months after adjusting for the presence of the 4 VDR genotypes and allele gene polymorphisms. Results: Overall, 277 participants, with a mean (±SD) age of 41 ± 12 and 204 (74%) of whom were female, were included in the study. We found no statistically significant differences in vitamin D metabolites or (epimers) between male and females or younger subjects compared to those over 40 years of age except in 7C4 BL (p < 0.05). There was a statistically significant difference in 1,25(OH)2D3 concentrations between subjects with and those without genotypes AG and the allele G SNP2_Taql VDR gene polymorphism. Vitamin D3 concentrations were also significantly lower in subjects with the CC SNP3_Apal gene polymorphism compared to those without the CC SNP3 gene. No statistically significant effects were seen on vitamin D epimers and metabolites concentration in response to supplements before or after adjusting for the presence of the 4 VDR genotypes and allele gene polymorphisms. Conclusions: The CC SNP3 gene had statistically significant influence on vitamin D3 levels. Vitamin D and/or calcium supplements, however, had no effects on vitamin D epimer and metabolite concentration before or after adjusting for the presence of the 4 VDR genotypes and alleles. [ABSTRACT FROM AUTHOR]

Background and Objectives: Alopecia areata (AA) is a tissue-specific immune-mediated disorder that affects hair follicles and the nail apparatus. Due to the collapse of hair follicle immune privilege in AA, hair loss ranges in severity from small, localized patches on the scalp to the loss of entire body hair. Although AA is of uncertain etiology, the disease has a common genetic basis with a number of other autoimmune diseases. Materials and Methods: To identify candidate genes that confer susceptibility to AA in the Jordanian population and further understand the disease background, we performed DNA genotyping using case–control samples of 152 patients and 150 healthy subjects. Results: While no significant result was observed in the ten single-nucleotide polymorphisms (SNPs), CLEC4D rs4304840 variants showed significant associations with AA development within our cohort (p = 0.02). The strongest associations were for the codominant and recessive forms of rs4304840 (p = 0.023 and p = 0.0061, respectively). Conclusions: These findings suggest that CLEC4D gene variants may contribute to AA pathogenesis among Jordanians. Further advanced genetic analysis and functional investigations are required to elucidate the genetic basis of the disease. [ABSTRACT FROM AUTHOR]

Midazolam is widely used for intravenous sedation. However, wide interindividual variability is seen in the sensitivity to midazolam. The association between genetic factors and interindividual differences in midazolam sensitivity remains unclear. The present study explored the association between common genetic variants and sedative and amnesic effects of midazolam. This prospective study included patients who were scheduled to undergo dental procedures under intravenous sedation. The sedative effect was evaluated using the Ramsay sedation scale 5 min after midazolam (0.05 mg/kg) administration. We employed two parallel approaches in this study: genome-wide approach and candidate gene approach. The γ-aminobutyric acid type A receptor subunit genes were selected as candidate genes. Multivariate linear regression analyses were performed to investigate the association between the Ramsay sedation scale and genetic variants. We also analyzed the association between the presence of anterograde amnesia and genetic variants using multivariate binominal logistic regression analyses. The analyses were adjusted for potential confounding factors. A total of 191 patients were included in the analyses. In the genome-wide association analyses, no significant association was found between the genetic variants and Ramsay scores. In the candidate gene analyses, the rs73247636 (dominant model: β = 0.72 [95% confidence interval, 0.34 to 1.10], P < 0.001) and rs56278524 (dominant model: β = 0.73 [0.37 to 1.10], P < 0.001) polymorphisms of the GABRB1 gene were significantly associated with Ramsay scores. Additionally, the rs73247636 (dominant model: odds ratio [OR] = 8.39 [2.36 to 29.85], P = 0.001) and rs56278524 (dominant model: OR = 15.26 [3.42 to 68.07], P < 0.001) polymorphisms were also significantly associated with the presence of anterograde amnesia. The rs73247636 and rs56278524 single-nucleotide polymorphisms of GABRB1 were associated with the sedative and amnesic effects of midazolam. [ABSTRACT FROM AUTHOR]

Coke oven emissions (COEs) contain a variety of polycyclic aromatic hydrocarbons (PAHs), which can cause damage to the human cardiovascular system. In addition, myocardial mitochondria are susceptible to damage in hypertensive patients. However, it is not clear whether genetic variation, in single nucleotide polymorphisms (SNPs) in PINK1 affects COEs exposure-induced abnormal blood pressure. We surveyed and tested 518 workers exposed to COEs and statistically analyzed them with SPSS 21.0 software. SBP was greater in the high-exposure group than in the low-exposure group. Generalized linear model analysis showed that the interaction of PINK1 rs3738136 (GA+AA) and COEs had an effect on SBP [β(95%CI) = -6.537(−12.072, −1.002), p = 0.021] and DBP [β(95%CI) = -4.811(−8.567, −1.056), p = 0.012]. This study is the first to identify the role of PINK1 rs3738136 in COE- induced abnormal blood pressure, and to prove that the abnormal blood pressure of workers is the result of environmental and genetic factors. [ABSTRACT FROM AUTHOR]

The accumulation of protoporphyrin IX in the liver caused by isoniazid and rifampicin through the disorder of heme biosynthesis was considered an important mechanism of anti‐tuberculosis drug‐induced liver injury (ATLI). Alanine synthase 1 (ALAS1) is a rate‐limiting enzyme in the process of heme synthesis. This study aimed to investigate the association between ALAS1 gene polymorphism, serum ALAS1 level, and the risk of ATLI. This study was a case‐control study including 58 ATLI cases and 192 controls. Four single nucleotide polymorphisms (SNPs) of the ALAS1 gene were selected for genotyping and serum ALAS1 concentrations were detected using ELISA kits. There was no significant difference in the genotype distribution of four SNPs between the ATLI cases and the controls under different genetic models. Patients carrying the GG genotype of SNP rs352163 in controls had higher baseline ALAS1 levels than those in ATLI cases (243.6 vs 290.2 ng/L, P = .034), and patients with baseline ALAS1 < 337.85 ng/L had a higher risk of ATLI than those with ALAS1 ≥ 337.85 ng/L (HR = 2.679, 95% CI: 1.360‐5.278, P = .004). Our findings indicated that the serum ALAS1 concentrations in the ATLI cases were lower than those in the controls, and the lower baseline ALAS1 levels can be associated with higher ATLI risk. [ABSTRACT FROM AUTHOR]

Pear (Pyrus spp.) is a major fruit crop in the Rosaceae family, and extensive efforts have been undertaken to develop elite varieties. With advances in genome sequencing technologies, single-nucleotide polymorphisms (SNPs) are commonly used as DNA markers in crop species. In this study, a large-scale discovery of SNPs was conducted using genotyping by sequencing in a collection of 48 cultivated pear accessions. A total of 256,538 confident SNPs were found on 17 chromosomes, and 288 SNPs were filtered based on polymorphic information content, heterozygosity rate, and genome distribution. This subset of SNPs was used to genotype an additional 144 accessions, consisting of P. pyrifolia (53), P. ussuriensis (27), P. bretschneideri (19), P. communis (26), interspecific hybrids (14), and others (5). The 232 SNPs with reliable polymorphisms revealed genetic variations between and within species in the 192 pear accessions. The Asian species (P. pyrifolia, P. ussuriensis, and P. bretschneideri) and interspecific hybrids were genetically differentiated from the European species (P. communis). Furthermore, the P. pyrifolia population showed higher genetic diversity relative to the other populations. The 232 SNPs and four subsets (192, 96, 48, and 24 SNPs) were assessed for variety identification. The 192 SNP subset identified 173 (90.1%) of 192 accessions, which was comparable to 175 (91.1%) from the 232 SNPs. The other three subsets showed 81.8% (24 SNPs) to 87.5% (96 SNPs) identification rates. The resulting SNPs will be a useful resource to investigate genetic variations and develop an efficient DNA barcoding system for variety identification in cultivated pears. [ABSTRACT FROM AUTHOR]

This study explored the polymorphism of the leucine aminopeptidase (LAP3) gene and its relationship with milk quality characteristics in Gannan yak. A cohort of 162 Gannan yak was genotyped utilizing the Illumina Yak cGPS 7K BeadChip, and the identified single nucleotide polymorphisms (SNPs) were evaluated for their association with milk protein, casein, lactose, and fat concentrations. The results showed that four SNPs (g.4494G > A, g.5919A > G, g.8033G > C, and g.15,615A > G) in the LAP3 gene exhibited polymorphism with information content values of 0.267, 0.267, 0.293, and 0.114, respectively. All four SNPs were in Hardy–Weinberg equilibrium (p > 0.05). The g.4494G > A and g.5919A > G SNPs were significantly associated with protein content (p < 0.05), with homozygous genotypes showing significantly higher protein content than heterozygous genotypes (p < 0.05). The g.8033G > C SNP was significantly associated with casein content, protein content, non-fat solids, and acidity (p < 0.05), with the CC genotype having significantly higher casein, protein, and non-fat solids content than the GG and GC genotypes (p < 0.05). The g.15,615A > G SNP was significantly associated with average fat globule diameter (p < 0.05). In general, the mutations within the LAP3 gene demonstrated a positive impact on milk quality traits in Gannan yak, with mutated genotypes correlating with enhanced milk quality. These results indicate that the LAP3 gene could be a significant or candidate gene affecting milk quality traits in Gannan yak and offer potential genetic markers for molecular breeding programs in this species. [ABSTRACT FROM AUTHOR]

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

Introduction: single nucleotide polymorphisms (SNPs) in exon 5 of the Glutathione-S-transferase Pi 1 (GSTP1) gene are directly associated with the progression and onset of leukemias. SNPs are common prognostic biomarkers for predicting and early onset of leukemia risk. The variant frequency of GSTP1 rs1695 (313 A>G) polymorphisms may affect various ethnic groups differently. In this study, the allelic frequency distribution of rs1695 (313 A>G) polymorphisms was assessed in the Saudi Arabian population and compared with other world populations. Material and Methods: Data were extracted from case-control studies in several ethnic groups using PubMed (Medline) and similar web databases. Results: The frequency of GSTP1 rs16955 (313 A>G) variant allele (G) was observed at 29.5% and different frequencies were significantly found in Egypt (p = 0.001), and India (p = 0.002). The prevalence of the frequency of GSTP1 rs16955 in the Saudi Arabian population was compared to that of other populations. The observed findings reveal a distinct pattern of GSTP1 rs1695 (313 A>G) polymorphism variant allele in the populations of Saudi Arabia, possibly due to differences in race. Conclusion: The observed findings can help assess the risk for the population harboring the risk allele of rs1695 (313 A>G) SNP and their subsequent susceptibility to leukemia. [ABSTRACT FROM AUTHOR]

BACKGROUND: Radioiodine-131 (I-131) therapy is the common postoperative adjuvant therapy for differentiated thyroid cancer (DTC) However, methods to evaluate the efficacy and toxicity of I-131 on DTC are still lacking. OBJECTIVE: To evaluate the association between vitamin D receptor (VDR) gene polymorphisms and the efficacy and toxicity of I-131 in DTC patients. METHODS: A total of 256 DTC patients who received I-131 therapy were enrolled. The patients were divided into effective group and ineffective group. 4 single nucleotide polymorphisms (SNPs) (rs7975232, rs731236, rs1544410 and rs10735810) of VDR were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) Cell counting kit-8 (CCK-8) and flow cytometry were used to detect the proliferation and apoptosis of thyroid cancer cells. RESULTS: Patients in effective group had more CC genotype of rs7975232 and GG genotype of rs10735810 compared with patients in ineffective group They were also independent factors for influencing the efficacy of I-131. PTC-1 and FTC-133 cells transfected with CC genotype of rs7975232 showed lower proliferative activity and higher apoptosis rate after being treated with I-131 In addition, patients with CC genotype at rs7975232 had fewer adverse reactions after I-131 treatment. CONCLUSIONS: VDR gene polymorphisms may be associated with the efficacy and toxicity of I-131 in DTC patients, which will help to personalize the treatment for patients. [ABSTRACT FROM AUTHOR]

Purpose: Individual responses to platinum-based treatment for Non-Small Cell Lung Cancer (NSCLC) are influenced by genetic polymorphisms, including Single Nucleotide Polymorphisms (SNPs). This study aimed to explore the role of ERCC2 in the Nucleotide Excision Repair (NER) pathway for platinum-based chemotherapy in NSCLC. While ERCC2 is widely studied, data for Southeast Asian populations are lacking. Addressing this gap could improve personalized treatment strategies for NSCLC in this demographic. Patients and Methods: This study recruited 82 NSCLC patients with wildtype mutations of EGFR at Dr. H.A. Rotinsulu Lung Hospital, Bandung, and Dharmais Cancer Hospital, Jakarta. Data were collected prospectively from whole blood samples and medical records, while the effectiveness of chemotherapy was assessed by evaluating the response using RECIST 1.1 criteria on fourth cycle of chemotherapy. Results: The results of this study showed the presence of genotype variation among the subjects, with frequency distribution as follows: AA genotype (82.9%), AC genotype (15.9%), and CC genotype (1.2%). The analysis of the association between ERCC2 rs13181 CC + AC versus AA with RECIST 1.1 yielded an odds ratio (OR) of 1.042 (95% CI: 0.292– 3.715; p=0.950). A multivariate analysis that included cancer stage and chemotherapy regimen as additional variables produced an adjusted odds ratio (aOR) of 0.970 (95% CI: 0.263– 3.568; p=0.963). Conclusion: This study did not find statistically significant associations between ERCC2 rs13181 polymorphisms and chemotherapy responses. However, this research highlights the presence of genetic variation within the Indonesian population, with the AA genotype being the most prevalent, which may influence chemotherapy responses. The results provided preliminary data and lay the foundation for future comprehensive cohort observational investigations. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is a disease characterized by increased blood glucose, formed as a result of impaired mechanisms of insulin binding to cells. DNA samples of patients with T2DM (N = 535) and healthy individuals (N = 475) were used. We identified the association of lncRNA gene loci LINC02227 rs2149954 (OR = 0.76, P = 0.0083, PFDR = 0.017), LINC00305rs2850711 (OR = 1.43, P = 0.0017, PFDR = 0.004), and CDKN2B-AS1 rs4977574 (OR = 0.70, P = 0.0001, PFDR = 0.0003) in an additive model with T2DM. The LINC00305 gene locus rs2850711 showed association with fasting glucose level (P = 0.023) and C-peptide level (P = 0.00001); LINC02227 rs2149954 and CDKN2B-AS1 rs4977574 loci showed association with hypertension. MALAT rs619586 gene polymorphism was associated with C-peptide (P = 0.017), LDL (P = 0.012), and total cholesterol levels (P = 0.01). CDKN2B-AS1 rs4977574 gene polymorphism showed association with C-peptide levels (P = 0.027). SNP LINC02227 rs2149954 was associated with obesity (P = 0.0011, PFDR = 0.008). MEG3 rs7158663 gene polymorphism was associated with post infarct cardiosclerosis (P = 0.02). ROC curve analysis showed that the studied loci and variables such as sex, age of subjects, and BMI level included in the construction of the risk calculation model could predict the development of T2DM with a sensitivity of 98.0% and specificity of 97.0%; the area under the curve (AUC) was 95.30% (95% CI 93.50–97.40). [ABSTRACT FROM AUTHOR]

Background: Periodontitis is a complex disease, and bacterial factors play a crucial role in its initiation. The contributions of genetic and epigenetic factors to the pathogenesis of periodontal disease are increasingly recognized. Single-nucleotide polymorphisms (SNPs) in various molecules, including cytokines, are of particular interest due to their established involvement in numerous diseases. This study investigates the influence of SNPs in the IL-10 gene at positions −592 (rs1800872) C>A and −1082 (rs1800896) T>C (also referred to as 1082A>G) on the severity of periodontitis in a cohort of Bulgarian patients. Methods: In the recent study, both clinical and paraclinical methodologies were employed to comprehensively assess the periodontal status of the participants. The genotypic characterization of IL-10 polymorphisms was performed by PCR RFLP analysis. Statistical analyses, including principal component analysis (PCA), were executed utilizing IBM SPSS Statistics Version 21. Results: We have established a statistically significant association between the presence of at least one A-allele in the patients' genotype and the incidence of severe periodontitis (p = 0.047). Conclusions: IL-10 single-nucleotide polymorphisms (SNPs) could be effectively considered as biomarkers for the severity of periodontitis. [ABSTRACT FROM AUTHOR]

Pregnancy-associated glycoproteins (PAGs) are a polygenic family with many scattered genes and pseudogenes resulting from the duplication or fusion of a pseudogene with expression beginning in the trophoblast during the peri-implantation period and continuing in the trophectoderm. In this study, single-nucleotide polymorphism (SNP) and insertion/deletion (InDels) in the open reading frame (nine exons) of crossbreed pigs are reported for the first time. Novel SNPs/InDels were researched using genomic DNA templates isolated from the leukocytes of crossbreed pigs (N = 25), which were amplified, gel-out-purified, and sequenced. Sixteen SNPs and one InDel (g.6961_6966 Ins TGCCAA) were identified in the crossbreed pigs. In silico analysis revealed that among 16 SNPs, only 10 SNPs cause amino acid (aa) substitutions, and InDel codes asparagine (N298) and alanine (A299). The results provide a novel broad-based database (main pattern) that will be critical for future research into the possible correlations between the SNP genotypes of the pPAG2-L subfamily in pigs of various breeds whose reproductive traits are known. [ABSTRACT FROM AUTHOR]

The methylenetetrahydrofolate reductase (MTHFR) gene 677C➔T polymorphism is capable of altering folate metabolism and can modify certain neoplasia risk. Reports have suggested that folate can have an influence on bone development and so it is of interest to know if the MTHFR 677C➔T polymorphism is associated with the malignant transformation process of this tissue. The polymorphism was determined in 55 patients with osteosarcoma and in 180 healthy individuals. Compared with C/T+C/C genotypes, a 3.7-fold reduction in osteosarcoma probability is possible with the T/T genotype (OR 0.27, CI 95% 0.07–0.82). Undoubtedly, further studies, utilizing large samples and carried out on different populations, are necessary to confirm these results. [ABSTRACT FROM AUTHOR]

The study assigned new germplasm, which includes populations and inbreds, to established heterotic groups using various approaches to broaden the existing genetic base while maintaining the heterotic pattern in pearl millet [Pennisetum glaucum (L.) R. Br.]. It utilized 13 pearl millet populations of African and Asian origins and 24 new inbred parents from ICRISAT's breeding program. Testers, both inbred and composite, were employed to categorize these materials into heterotic groups. Different sets of line × tester crosses were generated and evaluated during the rainy season at multiple locations in India. The pearl millet populations were assigned to heterotic group B (seed parental groups) (HGB1 and HGB2) and heterotic group R (pollinator parental groups) (HGR1 and HGR2) based on general combining ability (GCA) and specific combining ability effects. Composite testers were found to be more effective for the heterotic grouping of pearl millet populations. New inbred lines were classified into HGB and HGR based on GCA and hybrid performance using opposite heterotic group testers and also using genetic similarity obtained from genotype‐by‐sequencing data.The new germplasm classified into heterotic groups will help enhance the genetic gain for the long‐term success of pearl millet hybrid breeding programs. Core Ideas: There is significant variation observed in pearl millet germplasm owing to its combining ability patterns.The specific combining ability effect had shown to be useful in determining the heterotic grouping of the pearl millet populations.Heterotic group composite testers exhibited higher breeding efficiency in classifying new populations into heterotic groups.Testcross performance, general combining ability effect, and single nucleotide polymorphism based genetic similarity were helpful in assigning inbred lines to heterotic group.The introduction of new germplasm into heterotic group will broaden the genetic base and enhance genetic gain in hybrid breeding. [ABSTRACT FROM AUTHOR]

Our study aimed to investigate the associations between CXCL12 rs1029153, rs1801157, and rs2297630 single-nucleotide polymorphisms (SNPs), CXCL12 protein levels, MS prevalence, and clinical parameters. This study included 250 individuals diagnosed with MS and 250 sex- and age-matched healthy control individuals from Lithuania. The SNPs were genotyped with real-time PCR-based assays. The CXCL12 protein concentration was evaluated in serum using the ELISA method. Of the studied CXCL12 SNPs, we found that the rs1801157 CT genotype in the males was associated with 2.3 times reduced MS odds when compared with the CC genotype according to the overdominant and codominant models (p = 0.011 and p = 0.012, respectively). There was a tendency, which did not reach adjusted statistical significance, for a lower CXCL12 protein concentration in the healthy individuals with the rs1801157 CT genotype (p = 0.028). Sensory symptoms were rarer in the women with the rs1801157 TT genotype (p = 0.004); however, this genotype was also associated with a shorter MS disease duration (p = 0.007). CXCL12 rs1801157 was associated with reduced odds of MS occurrence in the male individuals. In women, rs1801157 was associated with a sensory symptom prevalence. [ABSTRACT FROM AUTHOR]

Betel quid (BQ) use disorder (BUD) is prevalent in many Asian countries, impacting approximately 600 million people. We conducted a randomized clinical trial to analyze the impact of MAOA genetic variations on the severity of BQ craving. This was measured using DSM-5 criteria and the Yale–Brown Obsessive–Compulsive Scale modified for betel quid use (Y-BOCS-BQ). Participants were grouped according to the severity of BUD and MAOA gene single-nucleotide polymorphism (SNP) rs5953210 genotypes. The Y-BOCS-BQ scores were assessed at baseline (week 0) and during follow-up at weeks 2, 4, 6, and 8. The AA genotype group showed significantly greater reductions in Y-BOCS-BQ at weeks 2 (p = 0.0194), 4 (p = 0.0078), 6 (p = 0.0277), and 8 (p = 0.0376) compared to the GG genotype group. Additionally, within the antidepressant group, the AA genotype showed significant reductions in the Y-BOCS-BQ scores at weeks 2 (p = 0.0313), 4 (p = 0.0134), 6 (p = 0.0061), and 8 (p = 0.0241) compared to the GG genotype. The statistical analysis revealed a significant interaction between the treatment and placebo groups based on MAOA genotypes, with the AA genotype in the treatment group exhibiting a more pronounced decrease in Y-BOCS-BQ score (p interaction <0.05) at week 6. Our study highlights the importance of considering genetic factors when developing personalized treatment plans for BUD. [ABSTRACT FROM AUTHOR]

Primary ovarian insufficiency (POI) can lead to menstrual disturbance, resulting in ovarian dysfunction before age 40. Prevalence of POI is usually less than 1%; however, ethnicity or population characteristics may affect prevalence. POI is a heterogeneous disease that results from abnormalities in immunological and hormonal factors. Genetic factors can also contribute to POI. Here, we examine FSHR, ESR1, and BMP15 polymorphisms in patients with POI, and controls. We examined a hormonal gene that is important for pregnancy, follicle-stimulating hormone receptor (FSHR), as well as estrogen receptor 1 (ESR1), and associated it with FSHR expression, ovulation rate, and bone morphogenetic protein 15 (BMP15). We examined 139 Korean patients under age 40 with POI, and 350 Korean control participants without POI. Genotyping was performed by a polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) and TaqMan assays. Each identified genotype was subjected to statistical analysis to determine the odds ratios (ORs) and 95% confidence intervals (CIs). In combination genotype analyses, FSHR rs6165 A > G combined with ESR1 rs9340799 A > G, AG/GG (OR: 5.693; 95% CI: 1.088–29.792), as well as FSHR rs6166 A > G combined with ESR1 rs9340799 C > T, AG/GG (OR: 5.940; 95% CI: 1.134–31.131), were significantly associated with POI prevalence. Furthermore, an FSHR rs6165 A > G and BMP rs17003221 C > T, AG/CC combination was associated with POI prevalence (OR: 1.874; 95% CI: (1.059–3.316; p-value: 0.031)). In meta-analysis, FSHR rs6165 AA vs. AG + GG is associated with POI (p = 0.0013), and ESR1 rs2234693 AA vs. AG + GG is also associated with POI (p = 0.0101). Here, we compared the genotypes of FSHR, ESR1, and BMP15 in patients with POI, and controls. We found significant differences in genotype combinations between polymorphisms in FSHR and other genes. Through meta-analysis, we found that ESR1 rs9340799 and rs2234693 are associated with POI prevalence, and that BMP15 rs17003221 increases POI risk. These findings help to improve POI diagnosis in Korean women. [ABSTRACT FROM AUTHOR]

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