title: No evidence for genetic association with the let-7 microRNA-binding site or other common KRAS variants in risk of endometriosis.
abstract: 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?
  
  
  CONCLUSIONS
  We found no evidence for association between endometriosis risk and rs61764370 or any other SNPs in KRAS.
  
  
  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.
  
  
  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.
  
  
  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.
  
  
  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.
  
  
  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.
  
  
  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.
authors.affiliation: Genetics and Computational Biology Division,  Queensland Institute of Medical Research,  Royal Brisbane Hospital, Locked Bag 2000, Brisbane, QLD 4029  Australia.
authors.forename: Hien T T
authors.initials: HT
authors.lastname: Luong
authors.forename: Dale R
authors.initials: DR
authors.lastname: Nyholt
authors.forename: Jodie N
authors.initials: JN
authors.lastname: Painter
authors.forename: Brett
authors.initials: B
authors.lastname: Chapman
authors.forename: Stephen
authors.initials: S
authors.lastname: Kennedy
authors.forename: Susan A
authors.initials: SA
authors.lastname: Treloar
authors.forename: Krina T
authors.initials: KT
authors.lastname: Zondervan
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
mesh_terms: D020413:3' Untranslated Regions; D016022:Case-Control Studies; D004715:Endometriosis / Q000235:genetics*; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human; D018631:ras Proteins