title: The association of genetic polymorphisms in sex hormone biosynthesis and action with insulin sensitivity and diabetes mellitus in women at midlife.
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), 17beta-hydroxysteroid dehydrogenase (17HSD) type 1, and the estrogen receptors-alpha (ESR1) and -beta (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.
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, California, USA.
authors.forename: Joan C
authors.initials: JC
authors.lastname: Lo
authors.forename: Xinhua
authors.initials: X
authors.lastname: Zhao
authors.forename: Angelo
authors.initials: A
authors.lastname: Scuteri
authors.forename: Sarah
authors.initials: S
authors.lastname: Brockwell
authors.forename: MaryFran R
authors.initials: MR
authors.lastname: Sowers
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics; D000328:Adult; D001141:Aromatase / Q000235:genetics; D003920:Diabetes Mellitus / Q000235:genetics* / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000235:genetics; D047629:Estrogen Receptor beta / Q000235:genetics; D005260:Female; D012739:Gonadal Steroid Hormones / Q000096:biosynthesis*; D006306:Health Surveys; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044469:Racial Groups
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D012739:Gonadal Steroid Hormones; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; D001141:Aromatase