title: Role of CYP1B1, MYOC, OPTN, and OPTC genes in adult-onset primary open-angle glaucoma: predominance of CYP1B1 mutations in Indian patients.
abstract: OBJECTIVE
  Mutations in the CYP1B1, MYOC, OPTN, and WDR36 genes result in glaucoma. Given its expression in the optic nerve, it is likely a mutation in the OPTC gene is also involved in initiating glaucoma. This study was designed to evaluate the involvement of the CYP1B1, MYOC, OPTN, and OPTC genes in the etiology of adult-onset primary open-angle glaucoma (POAG) found in 251 Indian patients.
  
  
  METHODS
  Blood samples were obtained from individuals for DNA isolation. A combination of polymerase chain reaction-single strand conformation polymorphism, allele-specific PCR, and DNA sequencing techniques were used to detect mutations in four genes. Four microsatellite markers from the CYP1B1 candidate region and three intragenic CYP1B1 single nucleotide polymorphisms (SNPs) were used to determine the origin of the most common CYP1B1 mutations.
  
  
  RESULTS
  Three previously known mutations (Pro193Leu, Glu229Lys, and Arg368His) and one novel (Met292Lys) mutation were found in the CYP1B1 gene. Frequencies of the most common mutations, Glu229Lys and Arg368His, in patients were 5.12% and 3.98%, respectively. The Glu229Lys and Arg368His mutations were also found in normal controls at frequencies of 5% and 2%, respectively, suggesting that these mutations might be polymorphic variants in our population. The absence of allele sharing for D2S177, D2S1346, D2S2974, and D2S2331 markers and three intragenic CYP1B1 SNPs in patients suggested multiple origins for the Glu229Lys and Arg368His variants. Two of 251 (0.8%) patients had the Gln48His mutation in MYOC. There was no difference in the frequency of a MYOC -83G>A promoter polymorphism between patients and controls. A novel OPTN mutation, Thr202Arg, was detected in one of 251 (0.4%) patients. The OPTN variant Met98Lys was detected in similar frequencies in patients and controls. No mutation was detected in OPTC. Taken together, 3.59% (9/251) of our POAG patients had mutations in the CYP1B1, MYOC, and OPTN genes.
  
  
  CONCLUSIONS
  This is the first report to document the involvement of the CYP1B1, MYOC, and OPTN genes in the etiology of POAG in the same set of Indian patients. Our study shows that mutations in these genes are rare in Indian POAG patients.
authors.affiliation: Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, India. arunk00@hotmail.com
authors.forename: Arun
authors.initials: A
authors.lastname: Kumar
authors.forename: Manjunath G
authors.initials: MG
authors.lastname: Basavaraj
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Gupta
authors.forename: Imteyaz
authors.initials: I
authors.lastname: Qamar
authors.forename: Abdullah Mahmood
authors.initials: AM
authors.lastname: Ali
authors.forename: Vineeta
authors.initials: V
authors.lastname: Bajaj
authors.forename: T K
authors.initials: TK
authors.lastname: Ramesh
authors.forename: D Ravi
authors.initials: DR
authors.lastname: Prakash
authors.forename: Jyoti S
authors.initials: JS
authors.lastname: Shetty
authors.forename: Syril K
authors.initials: SK
authors.lastname: Dorairaj
mesh_terms: D000368:Aged; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D018797:Cell Cycle Proteins; D065633:Cytochrome P-450 CYP1B1; D003598:Cytoskeletal Proteins / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005787:Gene Frequency; D014644:Genetic Variation; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D007194:India; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic; D011509:Proteoglycans / Q000235:genetics*; D035582:Transcription Factor TFIIIA / Q000235:genetics*; D000099179:Myocilin
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; D018797:Cell Cycle Proteins; D065633:Cytochrome P-450 CYP1B1; D003598:Cytoskeletal Proteins; D016326:Extracellular Matrix Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D026901:Membrane Transport Proteins; D011509:Proteoglycans; D035582:Transcription Factor TFIIIA; D000099179:Myocilin; C404108:OPTC protein, human; C409460:OPTN protein, human; C585496:CYP1B1 protein, human