title: Heterozygous CYP1B1 gene mutations in Spanish patients with primary open-angle glaucoma.
abstract: OBJECTIVE
  To investigate CYP1B1 gene mutations in Spanish patients with ocular hypertension (OHT) or primary open angle glaucoma (POAG).
  
  
  METHODS
  The two coding exons of CYP1B1 were screened for sequence alterations by direct PCR DNA sequencing in 37 and 82 unrelated Spanish subjects diagnosed with OHT and POAG, respectively. As a control we used a group of 93 subjects from whom OHT or glaucoma were ruled out.
  
  
  RESULTS
  We found three different predicted amino acid substitutions (Ala189Pro, Ala330Ser, and Ala443Gly) in three (8.1%) OHT subjects, and seven different mutations (Ser28Trp, Gly61Glu, Tyr81Asn, Gln144His, Arg145Trp, Glu229Lys, and Val409Phe) in nine (10.9%) glaucoma patients. These sequence variations showed higher frequencies in cases than in controls (as recently reported in French patients). They are predicted to produce a significant change in the amino acid sequence and affect conserved regions of the protein. All these missense mutations were found as heterozygots. In addition, four of them have been previously found in PCG and/or POAG patients, whereas the other six mutations (Ser28Trp, Gln144His, Arg145Trp, Ala189Pro, Ala330Ser, and Val409Phe) have not been previously described. Clinically, these mutations are associated with an age at diagnosis ranging from 12 to 58 years (mean 34.3 years) and from 48 to 77 years (mean 59.9 years) among OHT and glaucoma patients, respectively.
  
  
  CONCLUSIONS
  Heterozygous CYP1B1 mutations could confer increased susceptibility to the development of POAG in the Spanish population.
authors.affiliation: Area de Genetica, Facultad de Medicina/Centro Regional de Investigaciones Biomedicas (CRIB), Universidad de Castilla-La Mancha, Complejo Hospitalario Universitario de Albacete, Albacete, Spain.
authors.forename: María-Pilar
authors.initials: MP
authors.lastname: López-Garrido
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez-Sánchez
authors.forename: Francisco
authors.initials: F
authors.lastname: López-Martínez
authors.forename: José-Daniel
authors.initials: JD
authors.lastname: Aroca-Aguilar
authors.forename: Cristina
authors.initials: C
authors.lastname: Blanco-Marchite
authors.forename: Miguel
authors.initials: M
authors.lastname: Coca-Prados
authors.forename: Julio
authors.initials: J
authors.lastname: Escribano
mesh_terms: D000368:Aged; D019943:Amino Acid Substitution; D001189:Aryl Hydrocarbon Hydroxylases; D016022:Case-Control Studies; D017124:Conserved Sequence; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D009798:Ocular Hypertension / Q000235:genetics*; D010641:Phenotype; D013030:Spain
chemical_list: D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1