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Polycystic ovary syndrome is not associated with genetic variants that mark risk of type 2 diabetes

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Abstract

Polycystic ovary syndrome (PCOS) is a disorder of irregular menses, hyperandrogenism and/or polycystic ovary morphology. A large proportion of women with PCOS also exhibit insulin resistance, β-cell dysfunction, impaired glucose tolerance and/or type 2 diabetes (T2D). We therefore hypothesized that genetic variants that predispose to risk of T2D also result in risk of PCOS. Variants robustly associated with T2D in candidate gene or genome-wide association studies (GWAS; n = 56 SNPs from 33 loci) were genotyped in women of European ancestry with PCOS (n = 525) and controls (n = 472), aged 18–45 years. Metabolic, reproductive and anthropomorphic data were examined as a function of the T2D variants. All genetic association analyses were adjusted for age, BMI and ancestry and were reported after correction for multiple testing. There was a nominal association between variants in KCNJ11 and risk of PCOS. However, a risk score of 33 independent T2D-associated variants from GWAS was not significantly associated with PCOS. T2D variants were associated with PCOS phenotype parameters including those in THADA and WFS1 with testosterone levels, ENPP/PC1 with triglyceride levels, FTO with glucose levels and KCNJ11 with FSH levels. Diabetes risk variants are not important risk variants for PCOS.

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Acknowledgments

This work was supported by the National Institutes of Health U01 HD 4417 and 1R01HD065029, ADA 1-10-CT-57, and 1 UL1 RR025758 Harvard Clinical and Translational Science Center and M01-RR-01066 from the National Center for Research Resources.

Conflict of interest

The authors have no conflicts.

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Authors and Affiliations

  1. Department of Anaesthesia, Massachusetts General Hospital, Boston, MA, 02114, USA

    R. Saxena

  2. Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, 02114, USA

    R. Saxena

  3. Reproductive Endocrine Unit, BHX 511, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA

    C. K. Welt

Authors
  1. R. Saxena
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  2. C. K. Welt
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Correspondence to C. K. Welt.

Additional information

Communicated by Massimo Federici.

Clinical Trials Number: NCT00166569.

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Saxena, R., Welt, C.K. Polycystic ovary syndrome is not associated with genetic variants that mark risk of type 2 diabetes. Acta Diabetol 50, 451–457 (2013). https://doi.org/10.1007/s00592-012-0383-4

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  • DOI: https://doi.org/10.1007/s00592-012-0383-4

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