title: 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.
abstract: OBJECTIVE
  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.
authors.affiliation: 1INSERM, Unit 580, Paris, France. melkir@necker.fr
authors.forename: Rahma
authors.initials: R
authors.lastname: Melki
authors.forename: Nathalie
authors.initials: N
authors.lastname: Lefort
authors.forename: Antoine P
authors.initials: AP
authors.lastname: Brézin
authors.forename: Henri-Jean
authors.initials: HJ
authors.lastname: Garchon
mesh_terms: D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005602:France / Q000453:epidemiology; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D007429:Intraocular Pressure; D009898:Optic Disk / Q000473:pathology*; D009901:Optic Nerve Diseases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D014786:Vision Disorders / Q000235:genetics*; D058609:Visual Field Tests; D014794:Visual Fields
chemical_list: D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1