Association of the estrogen receptor-alpha gene with the metabolic syndrome and its component traits in African-American families: the Insulin Resistance Atherosclerosis Family Study

• Published in: Diabetes (New York, N.Y.) Vol. 56; no. 8; pp. 2135 - 2141
• Main Authors: Gallagher, Carla J, Langefeld, Carl D, Gordon, Candace J, Campbell, Joel K, Mychaleckyj, Josyf C, Mychalecky, Josyf C, Bryer-Ash, Michael, Rich, Stephen S, Bowden, Donald W, Sale, Michèle M
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.08.2007
• Subjects: Adiposity; Adult; African Americans - ethnology; African Americans - genetics; Atherosclerosis - complications; Atherosclerosis - ethnology; Atherosclerosis - genetics; Atherosclerosis - pathology; Diabetes Mellitus, Type 2 - ethnology; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - pathology; Estrogen; Estrogen Receptor alpha - genetics; Estrogen receptors; Female; Genetic aspects; Glucose - metabolism; Homeostasis; Humans; Insulin resistance; Insulin Resistance - ethnology; Insulin Resistance - genetics; Introns - genetics; Lipid Metabolism; Male; Metabolic Syndrome - complications; Metabolic Syndrome - ethnology; Metabolic Syndrome - genetics; Metabolic Syndrome - pathology; Polymorphism, Single Nucleotide - genetics; Receptors; Risk factors; Type 2 diabetes; United States
• ISSN: 0012-1797; 1939-327X; 1939-327X
• DOI: 10.2337/db06-1017

We previously detected an association between a region of the estrogen receptor-alpha (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. 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. 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). 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.