Gallagher, Carla J.;
Langefeld, Carl D.;
Gordon, Candace J.;
Campbell, Joel K.;
Mychalecky, Josyf C.;
Bryer-Ash, Michael;
Rich, Stephen S.;
Bowden, Donald W.;
Sale, Michèle M.
Association of the Estrogen Receptor-α Gene With the Metabolic Syndrome and Its Component Traits in African-American Families
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Media type:
E-Article
Title:
Association of the Estrogen Receptor-α Gene With the Metabolic Syndrome and Its Component Traits in African-American Families
Contributor:
Gallagher, Carla J.;
Langefeld, Carl D.;
Gordon, Candace J.;
Campbell, Joel K.;
Mychalecky, Josyf C.;
Bryer-Ash, Michael;
Rich, Stephen S.;
Bowden, Donald W.;
Sale, Michèle M.
Description:
<jats:p>OBJECTIVE— We previously detected an association between a region of the estrogen receptor-α (ESR1) gene and type 2 diabetes in an African-American case-control study; thus, we investigated this region for associations with the metabolic syndrome and its component traits in African-American families from the Insulin Resistance Atherosclerosis Family Study.</jats:p>
<jats:p>RESEARCH DESIGN AND METHODS— A total of 17 single nucleotide polymorphisms (SNPs) from a contiguous 41-kb intron 1–intron 2 region of the ESR1 gene were genotyped in 548 individuals from 42 African-American pedigrees. Generalized estimating equations were computed using a sandwich estimator of the variance and exchangeable correlation to account for familial correlation.</jats:p>
<jats:p>RESULTS— Significant associations were detected between ESR1 SNPs and the metabolic syndrome (P = 0.005 to P = 0.029), type 2 diabetes (P = 0.001), insulin sensitivity (P = 0.0005 to P = 0.023), fasting insulin (P = 0.022 to P = 0.033), triglycerides (P = 0.021), LDL (P = 0.016 to P = 0.034), cholesterol (P = 0.046), BMI (P = 0.016 to P = 0.035), waist circumference (P = 0.012 to P = 0.023), and subcutaneous adipose tissue area (P = 0.016).</jats:p>
<jats:p>CONCLUSIONS— It appears likely that ESR1 contributes to type 2 diabetes and CVD risk via pleiotropic effects, leading to insulin resistance, a poor lipid profile, and obesity.</jats:p>