Association of rs12997 variant in the ACVR1 gene: a member of bone morphogenic protein signaling pathway with primary open-angle glaucoma in a Saudi cohort.

We investigated the association between variants rs12997 in activin A receptor type I (ACVR1) and rs1043784 in BMP6 located in the 3' untranslated region, and primary open-angle glaucoma (POAG). The retrospective case-control study used TaqMan real-time PCR assay to genotype 400 subjects, including 150 patients with POAG and 250 controls. The minor 'G' allele of rs12997 in ACVR1 showed significant association with POAG (p=0.027, OR=1.39, 95% CI=1.03 to 1.87). Likewise, rs12997 genotypes showed moderate association with POAG in recessive (p=0.048, OR=1.80, 95% CI=1.01 to 3.20) and log-additive models (p=0.030, OR=1.39, 95% CI=1.03 to 1.87), but did not survive Bonferroni correction. Rs1043784 in BMP6 showed no associations. Furthermore, rs12997 G/G genotype significantly (p=0.033) increased the risk of POAG (twofolds) independent of age, sex and rs1043784 genotypes in regression analysis. However, clinical variables such as intraocular pressure and cup/disc ratio showed no association with both the polymorphisms. To conclude, the study shows a modest association between rs12997 in the ACVR1 gene, a member of the bone morphogenic protein signaling pathway and POAG. However, the results need further replication in large population-based cohorts and different ethnicities to validate its role as an important genetic biomarker.