Replication of association of a novel insulin receptor gene polymorphism with polycystic ovary syndrome

Mark O. Goodarzi, Yvonne V. Louwers, Kent D. Taylor, Michelle R. Jones, Jinrui Cui, Soonil Kwon, Yii Der I. Chen, Xiuqing Guo, Lisette Stolk, André G. Uitterlinden, Joop S.E. Laven, Ricardo Azziz

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


Objective: To evaluate association with polycystic ovary syndrome (PCOS) of 295 variants in 39 genes central to metabolic insulin signaling and glycogen synthase kinase 3β (GSK-3β) regulation, followed by replication efforts. Design: Case-control association study, with discovery and replication cohorts. Setting: Subjects were recruited from reproductive endocrinology clinics, and controls were recruited from communities surrounding the University of Alabama at Birmingham and Erasmus Medical Center, Rotterdam. Patient(s): A total of 273 cases with PCOS and 173 control subjects in the discovery cohort; and 526 cases and 3,585 control subjects in the replication cohort. All subjects were caucasian. Intervention(s): Phenotypic and genotypic assessment. Main Outcome Measure(s): Detection of 295 single-nucleotide polymorphisms (SNPs), PCOS status. Result(s): Several SNPs were associated with PCOS in the discovery cohort. Four insulin receptor (INSR) SNPs and three insulin receptor substrate 2 (IRS2) SNPs associated with PCOS were genotyped in the replication cohort. One INSR SNP (rs2252673) replicated association with PCOS. The minor allele conferred increased odds of PCOS in both cohorts, independent of body mass index. Conclusion(s): A pathway-based tagging SNP approach allowed us to identify novel INSR SNPs associated with PCOS, one of which confirmed association in a large replication cohort.

Original languageEnglish (US)
Pages (from-to)1736-1741.e11
JournalFertility and sterility
Issue number5
StatePublished - Apr 2011
Externally publishedYes


  • INSR
  • PCOS
  • SNP
  • replication

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology


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