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  • Title: Association of single-nucleotide polymorphisms in TLR4 gene and gene-environment interaction with primary open angle glaucoma in a Chinese northern population.
    Author: Liu H, Qi S, He W, Chang C, Chen Y, Yu J.
    Journal: J Gene Med; 2020 Jan; 22(1):e3139. PubMed ID: 31697008.
    Abstract:
    BACKGROUND: The present study aimed to investigate the association of several single nucleotide polymorphisms (SNPs) within the Toll-like receptor 4 (TLR4) gene and additional gene-environment interaction with primary open angle glaucoma (POAG) risk. METHODS: Tests for Hardy-Weinberg equilibrium in controls and haplotype analysis were performed using SNPstats (https://www.snpstats.net). Generalized multifactor dimensionality reduction (GMDR) was performed to test the interaction effects among four SNPs within the TLR4 gene and environmental factors. Logistic regression was performed to calculate the odds ratios (ORs) (95% confidence interval [CI]) for association between four SNPs within the TLR4 gene and POAG risk. RESULTS: The POAG risk was significantly higher in carriers with the T allele of rs4986791 and the T allele of rs2149356 within the TLR4 gene than in those with the wild-type genotype, adjusted ORs (95% CI) were 1.65 (1.23-2.12) and 1.70 (1.16-2.31). The GMDR model suggested a significant two-locus model (p = 0.0010) involving rs2149356 and alcohol drinking. Alcohol drinkers with the rs2149356-GT+TT genotype within the TLR4 gene have the highest POAG risk compared to never alcohol drinkers with the rs2149356-GG genotype (OR = 2.62; 95% CI = 1.48-3.78) after covariates adjustment. However, the study did not find a significant any-locus model involving SNP and smoking. In all samples, the haplotype rs2149356-G-rs7873784-C was observed most frequently in two groups (47.47% and 48.21% for the POAG patients and controls, respectively). The results also indicated that no significant haplotype was associated with POAG risk. CONCLUSIONS: The minor alleles of rs4986791 and rs2149356 within the TLR4 gene, as well as interaction between rs2149356 and alcohol drinking, were associated with an increased POAG risk.
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