title: Mutations in the CYP1B1 gene may contribute to juvenile-onset open-angle glaucoma.
abstract: OBJECTIVE
  Glaucoma is one of the leading causes of blindness in the world. Juvenile-onset open-angle is a subtype of glaucoma. In this context, we investigate the possible mutations in the promoter and coding regions of the CYP1B1 gene among patients suffering juvenile-onset open-angle glaucoma (JOAG).
  
  
  METHODS
  The CYP1B1 gene was analysed for mutations in 61 unrelated Taiwanese probands with JOAG and in 100 healthy control subjects. Genomic DNA was extracted from peripheral blood leukocytes and then subjected to PCR. The amplified products were screened for base mutations by autosequence. Next, data from the two groups were compared using the χ(2) test. Additionally, three-dimensional (3D) modelling of the human wild-type and p.R390H mutation was performed using SWISS-MODEL, an automated homology modelling program. Finally, the figure was prepared for the modelled structures by using the Accelrys ViewerLite 5.0 program.
  
  
  RESULTS
  Analysis results indicated two CYP1B1 mutations and five polymorphisms. The prevalence of CYP1B1 gene mutations in this study was 4.92% (3/61). The mutations included a missense mutation (p.Arg390His; 2/3) and a mutation in the 5'-untranslated region (c.1-313A>C; 1/3). Moreover, computer-assisted modelling revealed that this p.R390H mutation affects the intra-molecular interaction in the hydrogen-bonding interaction with Glu387 and Asn428, thus altering significantly the efficiency of the haem-binding and proper folding of the molecule.
  
  
  CONCLUSIONS
  As a result, the p.Arg390His mutation might affect the protein structure and, ultimately, the normal function of CYP1B1. Therefore, we suggest that the c.1169G>A (p.Arg390His) mutation of CYP1B1 may be a risk factor for the development of JOAG.
authors.affiliation: Tian-Sheng Memorial Hospital, Tong Kang, Pin-Tong, Taiwan.
authors.forename: C-C
authors.initials: CC
authors.lastname: Su
authors.forename: Y-F
authors.initials: YF
authors.lastname: Liu
authors.forename: S-Y
authors.initials: SY
authors.lastname: Li
authors.forename: J-J
authors.initials: JJ
authors.lastname: Yang
authors.forename: Y-C
authors.initials: YC
authors.lastname: Yen
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D020121:5' Untranslated Regions / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065633:Cytochrome P-450 CYP1B1; D004252:DNA Mutational Analysis; D017931:DNA Primers; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006801:Humans; D007429:Intraocular Pressure; D008969:Molecular Sequence Data; D009154:Mutation; D016366:Open Reading Frames / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D015995:Prevalence; D017434:Protein Structure, Tertiary
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D017931:DNA Primers; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1