Replication of association of a novel insulin receptor gene polymorphism with polycystic ovary syndrome - PubMed (original) (raw)

. 2011 Apr;95(5):1736-41.e1-11.

doi: 10.1016/j.fertnstert.2011.01.015.

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

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

Mark O Goodarzi et al. Fertil Steril. 2011 Apr.

Abstract

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.

Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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Conflict of interest statement

Declaration of Conflicts of Interest: M.O.G, Y.V.L., K.D.T., M.R.J., J.C., S.K., Y-D.I.C., X.G., L.S., A.G.U., and R.A. have nothing to declare. J.S.E.L. has received grants from Genovum, Merck Serono, Organon, SheringPlough, MSD and Serono.

Figures

Figure 1

Figure 1

Metabolic insulin signaling pathway genes genotyped in the discovery cohort. The protein products of the thirty nine genes that were genotyped in the discovery cohort are indicated. Names containing a slash indicate two isoforms encoded by two different genes. p = phosphate group. IP3 = phosphatidylinositol (3,4,5)-trisphosphate.

References

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