title: Tag SNPs detect association of the CYP1B1 gene with primary open angle glaucoma.
abstract: OBJECTIVE
  The cytochrome p450 family 1 subfamily B (CYP1B1) gene is a well known cause of autosomal recessive primary congenital glaucoma. It has also been postulated as a modifier of disease severity in primary open angle glaucoma (POAG), particularly in juvenile onset families. However, the role of common variation in the gene in relation to POAG has not been thoroughly explored.
  
  
  METHODS
  Seven tag single nucleotide polymorphisms (SNPs), including two coding variants (L432V and N543S), were genotyped in 860 POAG cases and 898 examined normal controls. Each SNP and haplotype was assessed for association with disease. In addition, a subset of 396 severe cases and 452 elderly controls were analyzed separately.
  
  
  RESULTS
  There was no association of any individual SNP in the full data set. Two SNPs (rs162562 and rs10916) were nominally associated under a dominant model in the severe cases (p<0.05). A common haplotype (AGCAGCC) was also found to be nominally associated in both the full data set (p=0.048, OR [95%CI]=0.83 [0.69-0.90]) and more significantly in the severe cases (p=0.004, OR [95%CI]=0.68 [0.52-0.89]) which survives correction for multiple testing.
  
  
  CONCLUSIONS
  Although no major effect of common variation at the CYP1B1 locus on POAG was found, there could be an effect of SNPs tagged by rs162562 and represented on the AGCAGCC haplotype.
authors.affiliation: Department of Ophthalmology, Flinders University, Adelaide, Australia. kathryn.burdon@flinders.edu.au
authors.forename: Kathryn P
authors.initials: KP
authors.lastname: Burdon
authors.forename: Alex W
authors.initials: AW
authors.lastname: Hewitt
authors.forename: David A
authors.initials: DA
authors.lastname: Mackey
authors.forename: Paul
authors.initials: P
authors.lastname: Mitchell
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Craig
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases; D016022:Case-Control Studies; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D003710:Demography; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005902:Glaucoma, Open-Angle / Q000201:enzymology* / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1