The American Journal of Medicine
Volume 119, Issue 9, Supplement 1 , Pages S69-S78, September 2006

The Association of Genetic Polymorphisms in Sex Hormone Biosynthesis and Action with Insulin Sensitivity and Diabetes Mellitus in Women at Midlife

  • Joan C. Lo, MD

      Affiliations

    • Division of Research, Kaiser Permanente Northern California, Oakland, California, USA, and Department of Medicine, University of California–San Francisco, San Francisco, California, USA
    • ,
  • Xinhua Zhao, MS

      Affiliations

    • Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
    • ,
  • Angelo Scuteri, MD, PhD

      Affiliations

    • Laboratory of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA, and Unità Operativa Geriatria, Italian National Research Center on Aging, Rome, Italy
    • ,
  • Sarah Brockwell, PhD

      Affiliations

    • Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
    • ,
  • MaryFran R. Sowers, PhD

      Affiliations

    • Department of Epidemiology, University of Michigan, Ann Arbor, Michigan, USA
    • Corresponding Author InformationRequests for reprints should be addressed to MaryFran R. Sowers, PhD, 339 East Liberty, Suite 310, School of Public Health, University of Michigan, Ann Arbor, Michigan 48104.

Abstract 

We evaluated associations of insulin sensitivity, metabolic syndrome, and diabetes mellitus with single nucleotide polymorphism (SNP) variants from sex hormone biosynthesis and action in women of 4 races/ethnicities. DNA was extracted from transformed cell samples of 1,538 women in the Study of Women’s Health Across the Nation (SWAN). African American, Caucasian, Chinese, and Japanese women in SWAN enrolled in the Sex Steroid Hormone Genetics Protocol from whom fasting glucose and insulin measures (for estimating insulin sensitivity), diabetes status, and metabolic syndrome classification were obtained. SNPs from the genes encoding aromatase (CYP 19), 17β-hydroxysteroid dehydrogenase (17HSD) type 1, and the estrogen receptors–α (ESR1) and –β (ESR2) were measured. The prevalence of metabolic syndrome was 20% in Chinese women, 22% in Japanese women, 28% in Caucasian women, and 43% in African American women. The prevalence of diabetes was 3% in Chinese women, 4% in Japanese women, 7% in Caucasian women, and 19% in African American women. Significant associations of CYP 19 genotypes and insulin sensitivity were observed in African American, Caucasian, and Japanese women. Selected ESR1 and ESR2 genotypes were associated with insulin sensitivity and metabolic syndrome only in Japanese and Chinese women. The strongest associations related 17HSD genotypes to diabetes in Caucasian women, with odds ratios ranging from 4.4 to 7.5 and confidence intervals that excluded the null value. We observed strong associations between variations in sex hormone biosynthesis and function genes with insulin sensitivity, the metabolic syndrome, and diabetes that varied by race/ethnicity. The strong association of 17HSD and diabetes in Caucasian women has not been previously reported and should be further investigated.

Keywords:  Diabetes mellitus , Genetics , Haplotype , 17-Hydroxysteroid dehydrogenase , Insulin sensitivity , Metabolic syndrome

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 The Study of Women’s Health Across the Nation (SWAN) and the SWAN Repository were supported by grants from the National Institutes of Health (NIH), Department of Health and Human Services, through the National Institute on Aging, the National Institute of Nursing Research, and the NIH Office of Research on Women’s Health (Grant Nos. AG017719, NR004061, AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, and AG012495). The Sex Steroid Hormone Genetics Protocol was supported by the SWAN Repository.This report is based on samples from the SWAN DNA Repository. Scientists interested in developing studies based on this resource can find a description of the SWAN Core Repository and DNA Repository and information on obtaining access to the resources at www.swanrepository.org.

PII: S0002-9343(06)00831-X

doi:10.1016/j.amjmed.2006.07.009

The American Journal of Medicine
Volume 119, Issue 9, Supplement 1 , Pages S69-S78, September 2006

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