title: Common variants in the CYP2C19 gene are associated with susceptibility to endometriosis.
abstract: OBJECTIVE
  To follow-up previous studies highlighting a possible role for cytochrome P450, family 2, subfamily C, 19 (CYP2C19) in susceptibility to endometriosis by searching for additional variants in the CYP2C19 gene that may be associated with the disease.
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  Academic research.
  
  
  METHODS
  The cases comprised 2,271 women with surgically confirmed endometriosis; the controls comprised 939 women with self-report of no endometriosis and 1,770 unscreened population samples.
  
  
  METHODS
  Sequencing of the CYP2C19 region and follow-up of 80 single nucleotide polymorphisms (SNPs) in two case-control samples.
  
  
  METHODS
  Allele frequency differences between cases and controls.
  
  
  RESULTS
  Sequencing of the CYP2C19 gene region resulted in the detection of a large number of known and novel SNPs. Genotyping of 80 polymorphic SNPs in 901 endometriosis cases and 939 controls resulted in study-wide significant association signals for SNPs in moderate or complete linkage disequilibrium with rs4244285, a functional SNP in exon 5 that abrogates CYP2C19 function through the creation of an alternative splice site. Evidence of association was also detected for another functional SNP in the CYP2C19 promoter, rs12248560, which was highlighted in our previous study.
  
  
  CONCLUSIONS
  Functional variants in CYP2C19 may contribute to endometriosis susceptibility in both familial and sporadic cases.
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. Electronic address: jodie.painter@qimrberghofer.edu.au.
authors.forename: Jodie N
authors.initials: JN
authors.lastname: Painter
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Dale R
authors.initials: DR
authors.lastname: Nyholt
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Lutz
authors.initials: L
authors.lastname: Krause
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Zhen Z
authors.initials: ZZ
authors.lastname: Zhao
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Brett
authors.initials: B
authors.lastname: Chapman
authors.affiliation: Mater Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Christine
authors.initials: C
authors.lastname: Zhang
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Sarah
authors.initials: S
authors.lastname: Medland
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Kennedy
authors.affiliation: Centre for Military and Veterans' Health, University of Queensland, Mayne Medical School, Queensland, Australia.
authors.forename: Susan
authors.initials: S
authors.lastname: Treloar
authors.affiliation: Genetic and Genomic Epidemiology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Krina
authors.initials: K
authors.lastname: Zondervan
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D016022:Case-Control Studies; D065731:Cytochrome P-450 CYP2C19; D004715:Endometriosis / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics*; D005091:Exons; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006801:Humans; D015810:Linkage Disequilibrium; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D022821:RNA Splice Sites; D012307:Risk Factors; D017422:Sequence Analysis, DNA
chemical_list: D022821:RNA Splice Sites; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19
keywords: CYP2C19; Endometriosis; association; pooled sequencing; rs12248560; rs4244285