A genetic variant in TMCO1 is strongly associated with primary open angle, primary angle closure and pseudoexfolation glaucoma

Abstract

Purpose: Despite the different etiology of primary open angle glaucoma (POAG), primary angle closure glaucoma (PACG) and pseudoexfoliative glaucoma (PEXG), several studies have suggested overlapping genetic risk factors for these forms of glaucoma. Therefore, the aim of this study was to evaluate the role of genetic variants recently associated with POAG in different types of glaucoma using POAG, PCAG and PEXG patient cohorts from Pakistan.

Methods: Six variants in CDKN2B-AS1 (rs4977756), CDKN2B (rs1063192), ATOH7 (rs1900004), CAV1 (rs4236601), TMCO1 (rs4656461) and SIX1 (rs10483727) were genotyped using Taqman assays. A total of 513 unrelated glaucoma patients (268 POAG, 125 PACG and 120 PEXG) and 233 healthy controls were included in the study. Genotypic and allelic associations were analyzed by Chi-squared tests.

Results: The frequency of the A allele of TMCO1 rs4656461 was significantly higher in POAG (90.5%; p<0.001; OR 2.90), PACG (90.0%; p<0.001; OR 2.75) and PEXG (91.7%; p<0.001; OR 3.36) patients compared to control individuals (76.6%). The T allele of ATOH7 rs1900004 was observed less frequently in PACG patients (24.4%; p=0.03; OR 0.69) compared to control individuals (31.8%). The A allele of CAV1 rs4236601 was found more frequently in POAG (26.3%; p=0.008; OR 1.49) compared to control individuals (19.3%)

Conclusions: The TMCO1 rs4656461 variant is strongly associated with POAG, PACG and PEXG in the Pakistani population. Our study was unable to confirm previous associations reported for variants in CDKN2B-AS1, CDKN2B and SIX1 with any type of glaucoma.

Keywords: 539 genetics • 613 neuro-ophthalmology: optic nerve