Association of single nucleotide polymorphisms (SNPs) downstream of Transmembrane and Coiled-Coil Domains 1 (TMCO1) with primary open angle glaucoma (POAG) in African-Americans (AA)

Abstract

Purpose : Previously, a genome wide association study (GWAS) has identified the SNP rs4656461, downstream of TMCO1, to be associated with POAG in Caucasians. We tested the hypothesis that this genomic region is associated with increased POAG susceptibility and traits in an AA cohort.

Methods : AA subjects recruited for the POAAGG study from the Scheie Eye Institute and its satellite sites in Philadelphia were included. Eight SNPs including and surrounding rs4656461 were sequenced from both POAAGG cases (n=1537) and controls (n=1570). Genomic DNAs were extracted from either saliva or blood samples and were used as templates for PCR, and then Sanger sequenced. Logistic regression analyses between each SNP and POAG disease status were performed while adjusting for age and sex. Associations between each SNP and POAG phenotypic parameters, including central corneal thickness, cup to disc ratio, intraocular pressure, and retinal nerve fiber layer thickness, were assessed by ANOVA.

Results : The SNP rs4657473 (C>T) was associated with POAG disease status; homozygous T genotype was protective against glaucoma (OR 0.20, 95% CI 0.09-0.42; p<0.001). No associations were found between TMCO1 variants and phenotypic traits.

Conclusions : Our results demonstrate that a TMCO1 genomic region that has been associated with POAG in Caucasians is also associated with POAG in an AA population. However, the individual SNP associated in our AA population has not previously been implicated in glaucoma. We were unable to find any correlations between TMCO1 genotype and quantitative POAG traits.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.