Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
24796765
TITLE
Common variants in the CYP2C19 gene are associated with susceptibility to endometriosis.
ABSTRACT
OBJECTIVE NlmCategory: 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.
DESIGN NlmCategory: METHODS
Case-control study.
SETTING NlmCategory: METHODS
Academic research.
SUBJECT(S) NlmCategory: 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.
INTERVENTION(S) NlmCategory: METHODS
Sequencing of the CYP2C19 region and follow-up of 80 single nucleotide polymorphisms (SNPs) in two case-control samples.
MAIN OUTCOME MEASURE(S) NlmCategory: METHODS
Allele frequency differences between cases and controls.
RESULT(S) NlmCategory: 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.
CONCLUSION(S) NlmCategory: CONCLUSIONS
Functional variants in CYP2C19 may contribute to endometriosis susceptibility in both familial and sporadic cases.
Copyright 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
DATE PUBLISHED
2014 Aug
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2013/10/16
revised 2014/04/10
accepted 2014/04/10
aheadofprint 2014/05/03
entrez 2014/05/07 06:00
pubmed 2014/05/07 06:00
medline 2014/09/30 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Painter JN Painter Jodie N JN QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. Electronic address: jodie.painter@qimrberghofer.edu.au.
Nyholt DR Nyholt Dale R DR QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Krause L Krause Lutz L QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Zhao ZZ Zhao Zhen Z ZZ QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Chapman B Chapman Brett B QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Zhang C Zhang Christine C Mater Medical Research Institute, Brisbane, Queensland, Australia.
Medland S Medland Sarah S QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Martin NG Martin Nicholas G NG QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Kennedy S Kennedy Stephen S Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
Treloar S Treloar Susan S Centre for Military and Veterans' Health, University of Queensland, Mayne Medical School, Queensland, Australia.
Zondervan K Zondervan Krina K Genetic and Genomic Epidemiology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
Montgomery GW Montgomery Grant W GW QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
INVESTIGATORS
JOURNAL
VOLUME: 102
ISSUE: 2
TITLE: Fertility and sterility
ISOABBREVIATION: Fertil. Steril.
YEAR: 2014
MONTH: Aug
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1556-5653
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Fertil Steril
COUNTRY: United States
ISSNLINKING: 0015-0282
NLMUNIQUEID: 0372772
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
084766 Wellcome Trust United Kingdom
085235 Wellcome Trust United Kingdom
MR/K011480/1 Medical Research Council United Kingdom
R01 HD050537 NICHD NIH HHS United States
R01HD50537 NICHD NIH HHS United States
WT084766/Z/08/Z Wellcome Trust United Kingdom
WT085235/Z/08/Z Wellcome Trust United Kingdom
GENERAL NOTE
KEYWORDS
KEYWORD
CYP2C19
Endometriosis
association
pooled sequencing
rs12248560
rs4244285
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Aryl Hydrocarbon Hydroxylases genetics
Case-Control Studies genetics
Cytochrome P-450 CYP2C19 genetics
Endometriosis genetics
Exons genetics
Female genetics
Gene Frequency genetics
Genetic Predisposition to Disease genetics
Heredity genetics
Humans genetics
Linkage Disequilibrium genetics
Pedigree genetics
Phenotype genetics
Polymorphism, Single Nucleotide genetics
Promoter Regions, Genetic genetics
RNA Splice Sites genetics
Risk Factors genetics
Sequence Analysis, DNA genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 RNA Splice Sites
EC 1.14.13.- Cytochrome P-450 CYP2C19
EC 1.14.14.1 Aryl Hydrocarbon Hydroxylases
EC 1.14.14.1 CYP2C19 protein, human
OTHER ID's
OTHERID SOURCE
NIHMS612479 NLM
PMC4150687 NLM