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

Joan C. Lo, Xinhua Zhao, Angelo Scuteri, Sarah Brockwell, MaryFran R. Sowers

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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.

Original languageEnglish
JournalAmerican Journal of Medicine
Volume119
Issue number9 SUPPL. 1
DOIs
Publication statusPublished - Sep 2006

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Gonadal Steroid Hormones
Genetic Polymorphisms
Insulin Resistance
Diabetes Mellitus
African Americans
Aromatase
Genotype
Women's Health
Single Nucleotide Polymorphism
Estrogen Receptors
Genes
Fasting

Keywords

  • 17-Hydroxysteroid dehydrogenase
  • Diabetes mellitus
  • Genetics
  • Haplotype
  • Insulin sensitivity
  • Metabolic syndrome

ASJC Scopus subject areas

  • Nursing(all)

Cite this

The Association of Genetic Polymorphisms in Sex Hormone Biosynthesis and Action with Insulin Sensitivity and Diabetes Mellitus in Women at Midlife. / Lo, Joan C.; Zhao, Xinhua; Scuteri, Angelo; Brockwell, Sarah; Sowers, MaryFran R.

In: American Journal of Medicine, Vol. 119, No. 9 SUPPL. 1, 09.2006.

Research output: Contribution to journalArticle

Lo, Joan C. ; Zhao, Xinhua ; Scuteri, Angelo ; Brockwell, Sarah ; Sowers, MaryFran R. / The Association of Genetic Polymorphisms in Sex Hormone Biosynthesis and Action with Insulin Sensitivity and Diabetes Mellitus in Women at Midlife. In: American Journal of Medicine. 2006 ; Vol. 119, No. 9 SUPPL. 1.
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