Association of variants in the FOXC1, ATXN2 and TXNRD2 genes with primary open angle glaucoma in a Brazilian population

Abstract

Purpose : Primary Open Angle Glaucoma (POAG) is the main cause of irreversible blindness worldwide, being described as a neurodegenerative disease of multifactorial etiology. Thus, the identification of genetic and environmental factors is of utmost importance for early diagnosis and to establish an appropriate clinical management. Multiethnic Genome Wide Association Studies (GWAS) identified single nucleotide variants (SNVs) in the FOXC1, ATXN2 and TXNRD2 genes that may be associated with the pathophysiology and endophenotypes of POAG. However, to our knowledge, these variants have not been investigated in admixed populations, such as the Brazilian population. The aim of this case-control study was to investigate the association of the variants rs2745572 (FOXC1), rs7137828 (ATXN2) and rs35934224 (TXNRD2) as risk factors for the development of POAG in a Brazilian cohort from the Southeast.

Methods : This study comprised 506 cases and 501 controls. Variants rs2745572 and rs35934224 were genotyped through Taqman® assay and validated by Sanger sequencing in 10% of the samples. Variant rs7137828 was genotyped exclusively by Sanger sequencing. Genetic association was estimated through Chi-Square and Logistic Regression tests.

Results : The case group was consisted of 50.99% males, while the control group was composed by 43.11% males (p=0.011). There was no statistical difference in age between cases and controls. The primary research outcome has revealed that the variant rs7137828 (ATXN2), was associated with an increased risk for development of POAG in the presence of the T allele (p=0.0025). Through multivariate logistic regression adjusted for gender, the TT genotype was associated with an increased risk for development of POAG compared to the CC genotype (p=0.006; OR=1.717; IC95%=1.169-2.535). There was no significant association of rs2745572 (FOXC1) and rs35934224 (TXNRD2) variants for alleles and genotypes with POAG.

Conclusions : Our data indicate an association of the variant rs7137828 in homozygosity as well as in the presence of the T allele with an increased risk for POAG in a Brazilian cohort. If validated in additional sub-populations from the country, this finding may enable the development of relevant strategies for early diagnosis of glaucoma in the future.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.