Association of a common coding polymorphism (N453S) of the cytochrome P450 1B1 (CYP1B1) gene with optic disc cupping and visual field alteration in French patients with primary open-angle glaucoma.

PURPOSE To investigate a role of common polymorphisms of the CYP1B1 gene in French patients with primary open-angle glaucoma (POAG). METHODS Six common CYP1B1 variants, 5 coding and one in promoter, were compared in 224 unrelated French Caucasian POAG patients, excluding those with a CYP1B1 mutation, and in 47 population-matched controls with a normal ophthalmic examination. Allelic associations were assessed with the D' and r2 parameters. An effect of the representative variants on subphenotypes, including the age and the intraocular pressure at diagnosis, the cup to disk ratio, and the visual field alteration, was tested by multivariate analyses. RESULTS Allele and haplotype frequencies were similar in patients and in controls. Five variants formed two groups with tightly correlated alleles while the sixth one, N453S, was independent. The age and the intraocular pressure at diagnosis were not influenced by any of the variants. In contrast, the 453*Serine allele was associated with decreased cupping of the optic disk (Odds ratio=0.32, 95% CI: 0.15-0.70; p=0.0036) and with a milder alteration of the visual field (p=0.025). CONCLUSIONS The common N453S coding variant of CYP1B1 is potentially a factor of severity in POAG patients.