Genetic risk for primary open-angle glaucoma

Abstract

PURPOSE: Primary open-angle glaucoma (POAG) is a common disease requiring early diagnosis and treatment to avoid asymptomatic visual field loss and eventual blindness. LMX1B mutations cause dominantly-inherited Nail-Patella syndrome in which approximately 33% of patients develop glaucoma. This study investigated the wider role of LMX1B in POAG. METHODS: The contribution of variation at the LMXIB locus to risk of glaucoma was investigated in a case-control genetic association study in 272 patients with high-tension glaucoma (HTG), 37 patients with normal-tension glaucoma (NTG), 58 patients with ocular hypertension (OHT), and 276 controls. RESULTS: Significant SNP associations were found for each patient group: rs7859156 was associated with HTG (P=0.0015; odds ratio [OR], 0.64) and OHT (P=0.0482; OR, 0.59); rs7854658 was associated with NTG (P=0.0041; OR, 0.30). A protective ATG haplotype (including rs7859156) was less prevalent in patients with raised intraocular pressure (22.7% in combined HTG+OHT group vs. 31.7% in controls; P=0.0005), and in patients with glaucoma (22.9% in combined HTG+NTG group vs. 31.7% in controls; P=0.0008). ATG carriers in these combined groups had a decreased risk of developing glaucoma (OR, 0.72 and OR, 0.73, respectively). A GCAGAC haplotype (including rs7854658) was also less prevalent in glaucoma patients (16.5% vs. 24.7%; P=0.0005) and carriers had a decreased risk of developing glaucoma (OR, 0.70). CONCLUSIONS: LMX1B haplotypes influence susceptibility to glaucoma in the general population, suggesting altered LMX1B function predisposes to glaucomatous damage and that this role may be independent of raised intraocular pressure.