Association of variant rs12997 in ACVR1 involved in transforming growth factor-ß signaling pathway with primary open-angle glaucoma

Abstract

Purpose : Transforming growth factor-β (TGF-β) may play a critical role in the pathogenesis of primary open-angle glaucoma (POAG). The study aimed to test the hypothesis that genetic variants in the genes involved in the TGF-β signaling pathway may also be associated with glaucoma. In a retrospective case-control study, we investigated variants rs12997 in ACVR1 (at chromosome 2q24.1) and rs1043784 in BMP6 (at chromosome 6p24.3) in POAG.

Methods : Genotyping was performed using TaqMan^® real-time PCR assays in a total of 400 subjects including 150 POAG patients and 250 controls. Statistical analysis was done to determine the association of variants with POAG and clinical indices like intraocular pressure and cup/disc ratio using SNPStats online tool and SPSS version 22 (IBM Inc. Chicago, IL, USA).

Results : The rs12997 minor ‘G’ allele was significantly associated with the risk of POAG (p=0.027, odds ratio [OR]=1.39, 95% confidence interval [CI]=1.03-1.87). Likewise, rs12997 genotypes showed a significant association with POAG in recessive (p=0.048, OR=1.80, 95% CI=1.01-3.20) and log-additive models (p=0.030, OR=1.39, 95% CI=1.03-1.87), but not after adjustment for age and sex. Genotype and allele frequencies of rs1043784 were not significantly different between POAG cases and controls. Binary logistic regression analysis showed a significant trend of rs12997 G/G genotype towards POAG outcome (p=0.056) independent of age and sex, but the significance was lost (p=0.637) after inclusion of rs1043784 genotypes in the model. Both the variants showed no association with POAG phenotypes such as intraocular pressure and cup/disc ratio.

Conclusions : Our results suggest that the polymorphism rs12997 in the ACVR1 gene involved in the TGF-β signaling pathway is significantly associated with POAG, supporting the role of the TGF-β pathway in POAG pathogenesis. Further studies would be needed to validate these results.

This is a 2020 ARVO Annual Meeting abstract.