Association of Functional ADRB1 (rs1801252) and ADRB2 (rs1042714) Polymorphisms with Primary Open-Angle Glaucoma in a Saudi Cohort

This case–control study investigated the association between β-adrenergic receptors, ADRB1 rs1801252 (A-to-G/Ser49Gly) and ADRB2 rs1042714 (C-to-G/Gln27Glu), polymorphisms and primary open-angle glaucoma (POAG) in a Saudi cohort. Genotyping of 418 participants (167 cases and 251 controls) was performed using real-time PCR assays. Analysis was performed among 412 participants with complete genotype data for both SNPs (163 cases and 249 controls). The ADRB1 rs1801252-G (Gly49) allele was significantly associated with increased POAG risk across allelic (adjusted odds ratio (OR) = 1.93; 95% confidence interval (CI) = 1.22–3.08; p = 0.005), dominant (adjusted OR = 2.13; 95% CI = 1.23–3.70; p = 0.007), and additive (adjusted OR per G allele = 1.93; 95% CI = 1.22–3.08; p = 0.005) models, surviving Bonferroni correction (α = 0.025). In contrast, ADRB2 rs1042714 showed no significant association under any model. Combined two-locus allelic analysis suggested a nominally increased risk for the C–G combined profile (ADRB2C + ADRB1G; OR = 1.91; p = 0.033). No significant genotype associations were observed with intraocular pressure or cup-to-disc ratio within the POAG cohort. These findings suggest that ADRB1 rs1801252 may contribute to POAG susceptibility in this population; replication in larger cohorts and targeted functional follow-up studies are warranted to elucidate pressure-independent mechanisms.