DPF3 polymorphisms increased the risk of pulmonary tuberculosis in the Northwest Chinese Han population.

PURPOSE: This study aimed to investigate the association between single nucleotide polymorphisms (SNPs) in DPF3 and susceptibility to pulmonary tuberculosis (PTB) in the Northwest Chinese Han population. METHODS: Genotyping of four DPF3 SNPs (rs10140566, rs75575287, rs202075571, and rs61986330) was performed using Agena MassARRAY from 488 PTB patients and 488 healthy controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression. Multifactor dimensionality reduction (MDR) analysis was employed to investigate the effect of SNP-SNP interactions on PTB risk. The GSE54992 dataset was analyzed using R software to ascertain DPF3 expression levels. RESULTS: Overall analysis revealed that rs202075571 (allele: OR = 1.31, p = 0.015; CC vs. TT: OR = 1.97, p = 0.049; dominant: OR = 1.33, p = 0.032) and rs61986330 (allele: OR = 1.38, p = 0.010; CA vs. CC: OR = 1.35, p = 0.044; dominant: OR = 1.40, p = 0.019) were associated with an increased PTB risk. Stratified analysis showed that rs10140566 was a PTB risk factor in females, those aged ≤40 and non-smokers, and rs202075571 was associated with PTB risk in individuals aged >40 and smokers, and rs61986330 was associated with PTB risk in males, those aged >40 and smokers. The four SNPs model demonstrated significant predictive potential for PTB risk. Furthermore, DPF3 exhibited higher expression in PTB compared to healthy controls. CONCLUSION: DPF3 polymorphisms (rs10140566, rs202075571, and rs61986330) are associated with an increased risk of PTB, providing valuable new insights into the mechanism of PTB.

Novel insight into the genetic signatures of altitude adaptation related body composition in Tibetans.

Background: The Tibetan population residing in high-altitude (HA) regions has adapted to extreme hypoxic environments. However, there is limited understanding of the genetic basis of body compositions in Tibetan population adapted to HA. Methods: We performed a genome-wide association study (GWAS) to identify genetic variants associated with HA and HA-related body composition traits. A total of 755,731 single nucleotide polymorphisms (SNPs) were genotyped using the precision medicine diversity array from 996 Tibetan college students. T-tests and Pearson correlation analysis were used to estimate the association between body compositions and altitude. The mixed linear regression identified the SNPs significantly associated with HA and HA-related body compositions. LASSO regression was used to screen for important SNPs in HA and body compositions. Results: Significant differences were observed in lean body mass (LBW), muscle mass (MM), total body water (TBW), standard weight (SBW), basal metabolic rate (BMR), total protein (TP), and total inorganic salt (Is) in different altitudes stratification. We identified three SNPs in EPAS1 (rs1562453, rs7589621 and rs7583392) that were significantly associated with HA (p < 5 × 10-7). GWAS analysis of 7 HA-related body composition traits, we identified 14 SNPs for LBM, 11 SNPs for TBW, 15 SNPs for MM, 16 SNPs for SBW, 9 SNPs for BMR, 12 SNPs for TP, and 26 SNPs for Is (p < 5.0 × 10-5). Conclusion: These findings provide insight into the genetic basis of body composition in Tibetan college students adapted to HA, and lay the foundation for further investigation into the molecular mechanisms underlying HA adaptation.

Association Between CYP24A1 Polymorphisms and Bladder Cancer Risk in the Chinese Han Population.

In this cohort of 217 bladder cancer patients and 484 healthy controls, we explored the association between CYP24A1 variants (rs2762934, rs1570669, rs6068816, rs2296241) and bladder cancer risk in the Chinese Han population. Utilizing the Agena MassARRAY system, we genotyped four selected CYP24A1 polymorphisms. Logistic regression revealed a significant association of rs2762934 and rs1570669 with elevated bladder cancer risk, while rs6068816 exhibited a protective effect. Bioinformatics analysis of CYP24A1 expression in normal and cancerous bladder tissues indicated higher expression in normal tissue. In conclusion, our findings highlight the potential role of CYP24A1 variants in bladder cancer susceptibility.

Impact of missense TSBP1 variants on the susceptibility to coronary heart disease.

BACKGROUND: A genome-wide association study has recognized C6orf10-BTNL2 polymorphism in coronary artery disease. The goal of this study was to explore the potential correlation of nine missense TSBP1 variants with coronary heart disease (CHD) risk in the Chinese Han population. METHODS: Nine TSBP1 missense single nucleotide polymorphisms (SNPs) were selected for genotyping by the Agena MassARRAY platform. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to analyze the contribution of TSBP1 SNPs to CHD predisposition by logistic regression models adjusted by age, sex, drinking, and smoking. The correlation of TSBP1 variants with clinical data in CHD patients was examined by Kruskal-Wallis test. RESULTS: rs9268368-C (p = 0.039, OR = 1.18, 95 % CI: 1.01-1.38) was related to an increased risk of CHD, while rs3749966-C (p = 0.032, OR = 0.49, 95 % CI: 0.25-0.96) and rs3129941-A (p = 0.011, OR = 0.74, 95 % CI: 0.59-0.93) might be protective factors against CHD occurrence in the Chinese Han population. We also observed the effects of demographic characteristics (age, sex, alcohol consumption, and smoking) and complications (hypertension and diabetes) on the interactive association of TSBP1 polymorphisms with CHD susceptibility. rs139993810 was related to the levels of high-density lipoprotein cholesterol (HDL-C, p = 0.030). CONCLUSIONS: Our findings determined the association of TSBP1 rs9268368, rs3749966, and rs3129941 with CHD occurrence in the Chinese Han population, and highlighted the influence of demographic characteristics and complications on the interactive association of TSBP1 polymorphisms with CHD risk.

miR-9-3p inhibits glioma cell proliferation and apoptosis by directly targeting FOXG1.

There is accumulating evidence indicating that microRNA (miR)-9-3p expression is abnormal in patients with glioma; however, the role of miR-9-3p in glioma remains unclear. In the present study, reverse transcription-quantitative PCR and immunohistochemical assays were conducted to assess miR-9-3p and forkhead box G1 (FOXG1) expression, respectively. A luciferase reporter assay was performed to confirm the target of miR-9-3p. Moreover, cell counting kit-8 and flow cytometry assays were used to assess proliferation and apoptosis, respectively. The present study demonstrated that miR-9-3p is significantly downregulated, and FOXG1 is significantly upregulated, in patients with glioma. miR-9-3p overexpression inhibited proliferation and increased the apoptosis of both U87MG and TG-905 cells. In addition, FOXG1 was identified as a direct target of miR-9-3p, and FOXG1 silencing enhanced the inhibitory effect of miR-9-3p on proliferation and apoptosis in U87 MG and TG-905 cells. In conclusion, the present results suggest that miR-9-3p may suppress malignant biological properties by targeting FOXG1. Thus, miR-9-3p may serve as a diagnostic target and novel prognostic marker in patients with glioma.

The association analysis between CYP24A1 genetic polymorphisms and the risk of ischemic stroke in Chinese Han population.

AIMS: Stroke is a complicated neurological disease and the second leading cause of death in the world. We aimed to investigate the association between CYP24A1 genetic polymorphisms and ischemic stroke risk. METHODS: In this case-control study, four single-nucleotide polymorphisms of CYP24A1 were selected and genotyped by MassARRAY platform in Chinese Han population. Odds ratios and 95% confidence intervals were calculated via logistic regression analysis with adjustment in genetic models. RESULTS: Our results indicated that CYP24A1 variant (rs1570669) was associated with the decreased risk of ischemic stroke (OR = 0.60, p < .001). Stratification analysis showed that the rs6068816 could enhance the ischemic stroke risk by 1.64 times (OR = 1.64, p = .028), while rs1570669 played protective role (OR = 0.63, p = .044) in age >64 years. The rs2762934 had an increased ischemic stroke susceptibility (OR = 1.62, p = .033); however, rs1570669 might reduce stroke risk (OR = 0.61, p = .015) in age ≤64 years. The rs1570669 depressed ischemic stroke susceptibility both in female and male patients (OR = 0.46, p = .002; OR = 0.69, p = .033, respectively), and rs2296241 would weaken the risk in male (OR = 0.63, p = .012). The rs1570669 was associated with decreased risk of ischemic stroke with hypertension (OR = 0.56, p = .042). CONCLUSION: Our study gave the evidences that CYP24A1 genetic polymorphisms were significantly associated with ischemic stroke patients, which would provide useful information of assessment or possible diagnostic markers for ischemic stroke.

Three SNPs of FCRL3 and one SNP of MTMR3 are associated with immunoglobulin A nephropathy risk.

PURPOSE: Immunoglobulin A nephropathy (IgAN) is determined by a combination of multiple genetic and environmental factors, but its etiology and pathogenesis are not well understood. We aim to determine whether variations in FCRL3 and MTMR3 correlate with IgAN risk indices in Chinese Han people. METHODS: Eight single nucleotide polymorphisms (SNPs) of FCRL3 and MTMR3 were genotyped, and association analysis was performed. A total of 426 patients with IgAN and 498 healthy individuals, serving as the control group, were recruited for this association study. RESULTS: There were significant associations between FCRL3 rs11264793 (OR = 0.78; 95 % CI = 0.63-0.98; p = 0.029), rs11264794 (OR = 0.81; 95 % CI = 0.67-0.98; p = 0.026) and rs7522061 (OR = 0.79; 95 % CI = 0.65-0.95; p = 0.012) and decreased risk of IgAN according to allele model results. Under genetic models, FCRL3 and MTMR3 were associated with the risk of IgAN. Interestingly, FCRL3 reduced the IgAN susceptibility only in females, while MTMR3 was a risk factor for IgAN only in males. In addition, FCRL3 rs11264793 and rs7522061 were significantly associated with a decreased risk of IgAN in different disease grades. Moreover, the haplotypes ACC (p = 0.02) and CTC (p = 0.017) of LD block rs11264794/rs7522061/rs11264799 in the FCRL3 gene were significantly associated with a decreased risk of IgAN. CONCLUSIONS: We suggest that three SNPs of FCRL3 were associated with a decreased risk of IgAN, while one SNP of MTMR3 was associated with an increased risk of IgAN in Chinese Han populations. These findings may be useful in the development of early prognostics for IgAN.

Vitamin D receptor gene associations with pulmonary tuberculosis in a Tibetan Chinese population.

BACKGROUND: The vitamin D receptor (VDR) mediates the immunological function of vitamin D3, which activates macrophages, and vitamin D deficiency has been linked to tuberculosis risk. Single nucleotide polymorphisms (SNPs) in VDR may influence the function of vitamin D and susceptibility to tuberculosis. METHODS: This study included 217 patients with pulmonary tuberculosis (PTB) and 383 healthy subjects in a Tibetan Chinese population living in and near Xi'an. Association analyses of SNPs in VDR were performed with the SPSS 17.0 statistical packages, SNP stats software, Haploview software package (version 4.2), and the SHEsis software platform. RESULTS: Our results revealed a correlation between three SNPs (rs11574143, odds ratio [OR]: 1.47, 95 % confidence interval [CI]: 1.11 - 1.94, p = 0.006, p-adjust = 0.030; rs11574079, OR: 0.48, 95 % CI: 0.25 - 0.92, p = 0.023, p-adjust = 0.115; rs11168287, OR: 2.55, 95 % CI: 2.00 - 3.25, p = 1.730E-14, p-adjust = 0.865E-13) and PTB based on Chi-square tests. We observed the allele "A" of rs11574143 and rs11168287 increased the PTB risk and the allele "A" of rs11574079 provided a protective effect against PTB. CONCLUSIONS: The goal of this study was the identification of putative associations between five SNPs (rs11574143, rs7975232, rs11574079, rs3819545 and rs11168287) in VDR and susceptibility to PTB. Our findings demonstrated associations between VDR polymorphisms and PTB development.