AFAP1 (rs4619890) and TMCO1 (rs2814471) variants as risk factors for primary open-angle glaucoma development in a Brazilian cohort

Abstract

Purpose : Primary Open Angle Glaucoma (POAG) stands as the leading cause of irreversible blindness worldwide, being described as an asymptomatic and neurodegenerative disease of multifactorial etiology. Despite several molecular insights into POAG genetics, studies in admixed populations, such as Brazilians, remain limited. In this context, multiethnic Genome-Wide Association Studies (GWAS) reported the rs4619890 (AFAP1) and rs2814471 (TMCO1) single nucleotide variants (SNVs) as possible risk factors for POAG pathophysiology and/or endophenotypes development in other cohorts. The aim of this cross-sectional case–control study was to appraise the association of the aforementioned SNVs as risk or protective factors for POAG development in a South and Southeastern Brazilian cohort.

Methods : This study comprised 447 POAG patients and 444 controls. Both Variants were genotyped using Taqman® assays and validated by Sanger sequencing (10% of the samples). All demographic and genetic association data were estimated through logistic regression tests adjusted by gender and sex (P<0.05).

Results : The case/control cohorts consisted of 48.95% and 43.02% females, respectively (p=0.0148). There was no statistical difference in age between groups. The logistic regression outcomes revealed an association between rs4619890 in homozygosity (GG; p=0.0000), and the rs2814471 in heterozygosity (CT; p=0.0010) as risk factors for POAG development in this Brazilian cohort. Cases and controls were in Hardy-Weinberg Equilibrium for the rs4619890 (p=0.7081 and 0.4186), and rs2814471 (p=0.0582 and 0.0809) loci, respectively.

Conclusions : Our data suggest an association of the rs4619890 (AFAP1) and rs2814471 (TMCO1) SNVs with increased risk for POAG pathogenesis in a Brazilian population from the South and Southeast. On the premise of additional validation in other cohorts, further insights regarding the genetic profile of the glaucoma pathogenesis could be accomplished, contributing to polygenic risk score investigations and other functional validations, given the valuable resource that the Brazilian genetic profile represents for complex trait mapping in humans.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.