Background: Primary open-angle glaucoma (POAG), the world's main cause of irreversible blindness, is an asymptomatic and neurodegenerative disease of multifactorial etiology with ethnic and geographic disparities. Multiethnic genome-wide association studies (GWAS) identified single nucleotide variants (SNVs) in ATXN2, FOXC1, and TXNRD2 loci as risk factors for POAG pathophysiology and/or endophenotypes. The aim of this case-control study was to investigate the association of the variants rs7137828 (ATXN2), rs2745572 (FOXC1), and rs35934224 (TXNRD2), as risk factors for POAG development, additionally to rs7137828 association with glaucoma clinical parameters in a Brazilian cohort from the Southeast and South regions.
Methods: This investigation comprised 506 cases and 501 controls. Variants rs2745572 and rs35934224 were genotyped through TaqMan® assays and validated by Sanger sequencing. Variant rs7137828 was genotyped exclusively by Sanger sequencing.
Results: The primary research outcome revealed that the variant rs7137828 (ATXN2) was associated with an increased risk for the development of POAG in the presence of the TT genotype compared to the CC genotype (p = 0.006; Odds Ratio [OR] = 1.717; Confidence Interval [CI] 95% = 1.169-2.535). There was no significant association of rs2745572 and rs35934224 genotypes with POAG. The CT genotype of the rs7137828 was associated with the vertical cup-to-disk ratio (VCDR) (p = .023) but not with the age at diagnosis or the mean deviation.
Conclusion: Our data indicate the rs7137828 associated with increased risk for the development of POAG and VCDR in a Brazilian cohort. If validated in additional populations, these findings may enable the development of relevant strategies for early diagnosis of glaucoma in the future.
Keywords: ATXN2; FOXC1; Primary Open Angle Glaucoma (POAG); Single Nucleotide Variant (SNV); TXNRD2.