Association of single-nucleotide polymorphisms in non-coding regions of the TLR4 gene with primary open angle glaucoma in a Mexican population.

Background: Toll-like receptor 4 (TLR4) non-coding polymorphisms are associated to primary open angle glaucoma (POAG), normal tension glaucoma, and pseudoexfoliation glaucoma. This study was performed to determine whether non-coding single nucleotide polymorphisms (SNPs) in theTLR4gene contribute to POAG in a Mexican population. Material and methods: A total of 187 unrelated Mexican patients with POAG and 109 control subjects were included. Allelic, genotypic, and haplotypic diversity was assessed for the non-coding polymorphisms rs11536889, rs1927911, rs12377632, and rs2149356 of theTLR4gene. Genotyping of target SNPs was performed by 5′ exonuclease allelic discrimination assays. Results: Strong linkage disequilibrium was observed among the SNPs (D’> 0.818), which were located in one haplotype block. The rs11536889 polymorphism was not associated to POAG in any case. The frequency of the minor allele of rs2149356 was significantly higher in the glaucoma group, conferring an increased risk of POAG (p= 0.0018, OR = 1.803, 95% CI 1.2556–2.5890) whereas minor allele of rs12377632 was significantly lower, attributing a protective effect (p= 0.0001, OR = 0.6662, 95% CI 0.4753–0.9339). Subjects with genotypes carrying the minor allele of rs1927911 and rs2149356 shown an increased risk for POAG (p= 0.03, OR = 1.78, 95% CI 1.10–2.87, andp< 0.0004, OR =2.62, 95%CI 1.61–4.27 respectively). Finally, we found significant risk haplotypes. The GTT haplotype (constituted by rs1927911, rs12377632, and rs2149356) reached the higher OR (p= 0.0026, OR = 4.70, 95% CI 1.73–12.77). Conclusions: We have identified intronicTLR4SNPs as genetic susceptibility alleles for POAG in a Mexican population. Our findings support the association of theTLR4gene with POAG. [ABSTRACT FROM AUTHOR]