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RAMSES ROSALES DIAZ, JOSE NAVARRO-PARTIDA, BEATRIZ ALVARADO-CASTILLO, ABRIL BERNARDETTE MARTINEZ-RIZO, JESUS BERNARDINO VELAZQUEZ-FERNANDEZ, ARTURO SANTOS; Pro-apoptotic TLR4 polymorphisms D299G and T399I are related to primary open angle glaucoma in Mexican population. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2129.
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© ARVO (1962-2015); The Authors (2016-present)
Toll-like receptor 4 (TLR4) is a transmembrane receptor that mediates immune responses to exogenous and endogenous ligands. Previously, the single nucleotide polymorphisms (SNPs) D299G (rs4986790) and T399I (rs4986791) in TLR4 gene have been related to apoptosis of activated hepatic stellate cells. The underlying mechanism involves the reduction of phospho-ERK and Bcl-2. Therefore, this study was undertaken to investigate whether pro-apoptotic TLR4 D299G and T399I are associated with primary open angle glaucoma (POAG) in Mexican population.
One hundred eighty-seven unrelated Mexican patients with POAG (94 men and 95 women; mean age 66.49 ± 14.3 years) and 109 control subjects (40 men and 69 women; age, 63.28 ± 7.93 years) were included. SNPs D299G and T399I were genotyped by a Taqman® Allelic Discrimination Assay. Allelic, genotypic and haplotypic diversity were assessed between cases and control subjects.
Strong linkage disequilibrium was observed among the SNPs (D’= 0.8692), which were in one haplotype block. With respect to allelic analysis, the minor allele of D299G conferred the highest increased risk of POAG (OR= 4.47, 95% CI= 1.46-13.70, P= 0.0054) whereas T399I was related to an OR=3.506 (95% CI=1.2719-9.6623, P=0.0262). Considering the dominant model, subjects carrying the minor allele of D299G and T399I had a significant increased risk for POAG with OR of 4.47 (P=0.054, 95% CI= 1.30-15.35) and 3.5 respectively (P= 0.012, 95% CI= 1.17-10.44). Haplotype analysis was non-significant.
TLR4 coding SNPs D299G and T399I might be used as genetic susceptibility alleles for POAG in Mexican population. Our findings support that these TLR4 SNPs could be promoting a pro-apoptotic environment that conduces to neurodegeneration in the pathophysiology of glaucoma.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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