CYP1B1 mutations in French patients with early–onset primary open–angle glaucoma

Abstract

Abstract: : Purpose: To investigate an association with primary open–angle glaucoma (POAG) of mutations of the CYP1B1 gene, a member of the cytochrome P450 gene family that is a major cause of primary congenital glaucoma (PCG). This gene was also previously shown to modify MYOCILIN (MYOC) expression in a family with MYOC–linked juvenile–onset glaucoma, being associated with an earlier onset of disease in MYOC mutation carriers. Methods: 236 unrelated French Caucasian patients with POAG (median age at diagnosis, 48 ; range, 6–81) were investigated. Polymorphism of the CYP1B1 coding region was characterized by denaturing high performance liquid chromatography and direct sequencing. A previous screen had disclosed a MYOC mutation in 17 patients. Results: Eleven (4.6%) patients carried one or two mutated CYP1B1 gene(s) and showed a juvenile or middle–age onset of disease (median age at diagnosis, 40 years, range, 13–60), significantly earlier than noncarrier patients (P = 0.023 for the Mann–Whitney test). Apart from one, all mutations detected in these POAG patients were previously associated with PCG. The novel mutation, Tyr81Asn, affects an evolutionarily conserved residue in the cytochrome P450 family and was observed in two unrelated patients but not in 197 controls. None of the CYP1B1 mutation carriers harbored a MYOC mutation. Conclusions: CYP1B1 mutations may provide a significant risk for early–onset POAG and modify glaucoma phenotype also in patients who do not carry a MYOC mutation.

Keywords: genetics • gene modifiers • enzymes/enzyme inhibitors