Genetic Epidemiology, Translational Neurogenomics, Psychiatric 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
23010532
TITLE
No evidence for genetic association with the let-7 microRNA-binding site or other common KRAS variants in risk of endometriosis.
ABSTRACT
STUDY QUESTION NlmCategory: OBJECTIVE
Is there a contribution of the minor allele at the KRAS single nucleotide polymorphism (SNP) rs61764370 in the let-7 microRNA-binding site to endometriosis risk?
SUMMARY ANSWER NlmCategory: CONCLUSIONS
We found no evidence for association between endometriosis risk and rs61764370 or any other SNPs in KRAS.
WHAT IS KNOWN ALREADY NlmCategory: BACKGROUND
The rs61764370 SNP in the 3' untranslated region of the KRAS gene is predicted to disrupt a complementary binding site (LCS6) for the let-7 microRNA, and was recently reported to be at a high frequency (31%) in 132 women of varying ancestry with endometriosis compared with frequencies in a database of population controls (up to 7.6% depending on ancestry), suggesting a strong effect of this KRAS SNP in the aetiology of endometriosis.
STUDY DESIGN, SIZE AND DURATION NlmCategory: METHODS
This was a case-control study with a total of 11 206 subjects. The study was performed between February 2012 and July 2012. PARTICIPANTS/MATERIALS, SETTINGAND METHODS: We first investigated a possible association between common markers in KRAS and endometriosis risk from our genome-wide association (GWA) data in 3194 surgically confirmed endometriosis cases and 7060 controls of European ancestry. Although rs61764370 was not genotyped on the GWA arrays, five SNPs typed in the study were highly correlated with this variant. The rs61764370 and two SNPs highly correlated with rs61764370 were then genotyped in 933 endometriosis cases and 952 controls using the Sequenom MassARRAY platform.
MAIN RESULTS AND THE ROLE OF CHANCE NlmCategory: RESULTS
There was no evidence for an association between rs61764370 and endometriosis risk P = 0.411 and odds ratio = 1.10 (95% confidence intervals: 0.88-1.36). We also found no evidence for an association between the highly correlated SNP rs17387019 and endometriosis. Their minor allele frequencies in cases and controls were of 0.087-0.091 similar to the population frequency reported previously for this variant in controls. Analyses of endometriosis cases with revised American Fertility Society stage III/IV disease also showed no evidence for an association between these SNPs and endometriosis risk.
LIMITATIONS AND REASONS FOR CAUTION NlmCategory: CONCLUSIONS
The GWA and genotyped data sets were not independent since individuals and cases from some families overlap. Controls in our GWA study were not screened for endometriosis.
WIDER IMPLICATIONS OF THE FINDINGS NlmCategory: CONCLUSIONS
The key SNP, rs61764370, was genotyped in a subset of samples. Our results do not support the suggestion that carrying the minor allele at rs61764370 contributes to a significant number of endometriosis cases and rs61764370 is, therefore, unlikely to be a useful marker of endometriosis risk.
STUDY FUNDING/COMPETING INTEREST(S) NlmCategory: BACKGROUND
The research was funded by grants from the Australian National Health and Medical Research Council and Wellcome Trust. None of the authors has competing interests for the study.
DATE PUBLISHED
2012 Dec
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2012/09/25
entrez 2012/09/27 06:00
pubmed 2012/09/27 06:00
medline 2013/04/30 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Luong HT Luong Hien T T HT Genetics and Computational Biology Division, Queensland Institute of Medical Research, Royal Brisbane Hospital, Locked Bag 2000, Brisbane, QLD 4029 Australia.
Nyholt DR Nyholt Dale R DR
Painter JN Painter Jodie N JN
Chapman B Chapman Brett B
Kennedy S Kennedy Stephen S
Treloar SA Treloar Susan A SA
Zondervan KT Zondervan Krina T KT
Montgomery GW Montgomery Grant W GW
INVESTIGATORS
JOURNAL
VOLUME: 27
ISSUE: 12
TITLE: Human reproduction (Oxford, England)
ISOABBREVIATION: Hum. Reprod.
YEAR: 2012
MONTH: Dec
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN:
ISSNTYPE:
MEDLINE JOURNAL
MEDLINETA: Hum Reprod
COUNTRY: England
ISSNLINKING: 0268-1161
NLMUNIQUEID: 8701199
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
076113 Wellcome Trust United Kingdom
084766 Wellcome Trust United Kingdom
085235 Wellcome Trust United Kingdom
085475 Wellcome Trust United Kingdom
090532 Wellcome Trust United Kingdom
WT084766/Z/08/Z Wellcome Trust United Kingdom
WT085235/Z/08/Z Wellcome Trust United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
3' Untranslated Regions
Case-Control Studies
Endometriosis genetics
European Continental Ancestry Group genetics
Female genetics
Genes, ras genetics
Genome-Wide Association Study genetics
Humans genetics
MicroRNAs metabolism
Polymorphism, Single Nucleotide metabolism
ras Proteins genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 3' Untranslated Regions
0 MicroRNAs
0 mirnlet7 microRNA, human
EC 3.6.5.2 ras Proteins
OTHER ID's
OTHERID SOURCE
PMC3501245 NLM