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

摘要

Purpose: To investigate a role of common polymorphisms of theCYP1B1 gene in French patients with primary open-angle glaucoma(POAG).Methods: Six common CYP1B1 variants, 5 coding and one inpromoter, were compared in 224 unrelated French Caucasian POAG patients,excluding those with a CYP1B1 mutation, and in 47 population-matchedcontrols with a normal ophthalmic examination. Allelic associations wereassessed with the D' and r2 parameters. An effect of therepresentative variants on subphenotypes, including the age and theintraocular pressure at diagnosis, the cup to disk ratio, and the visualfield alteration, was tested by multivariate analyses.Results: Allele and haplotype frequencies were similar in patientsand in controls. Five variants formed two groups with tightly correlatedalleles while the sixth one, N453S, was independent. The age and theintraocular pressure at diagnosis were not influenced by any of thevariants. In contrast, the 453*Serine allele was associated withdecreased 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 ispotentially a factor of severity in POAG patients.