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Association of the Estrogen Receptor Alpha gene with the Metabolic Syndrome and its component traits in African American families: The IRAS Family Study

¹Department of Biochemistry,
²Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC;
³Department of Health Evaluation Sciences, Penn State College of Medicine, Hershey, PA, Hershey, PA;
⁴Division of Public Health Sciences,
⁵Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC;
⁶Center for Public Health Genomics,
⁷Department of Public Health Sciences, University of Virginia, Charlottesville, VA;
⁸Division of Endocrinology, Diabetes and Metabolism, David Geffen School of Medicine, UCLA, Los Angeles, CA;
⁹Department of Medicine,
¹⁰Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA.

Correspondence: msale{at}virgnia.edu

Key Words: Estrogen • Receptor(s) • Genetic Susceptibility • Metabolic Syndrome

Objective:We previously detected an association between a region of the estrogen receptor (ESR1) gene and type 2 diabetes (T2DM) in an African American (AA) case-control study, and investigated this region for associations with Metabolic Syndrome and its component traits in AA families from the IRAS Family Study.

Research Design and Methods:Seventeen SNPs from a contiguous 41 kb intron 1 -- intron 2 region of the ESR1 gene were genotyped in 548 individuals from 42 AA pedigrees. Generalized estimating equations were computed using a sandwich estimator of the variance and exchangeable correlation to account for familial correlation.

Results:Significant associations were detected between ESR1 SNPs and Metabolic Syndrome (P = 0.005 -- P = 0.029), T2DM (P = 0.001), insulin sensitivity (P = 0.0005 -- P = 0.023), fasting insulin (P = 0.022 -- P = 0.033), triglycerides (P = 0.021), LDL (P = 0.016 -- P = 0.034), cholesterol (P = 0.046), BMI (P = 0.016 -- P = 0.035), waist circumference (P = 0.012 -- P = 0.023), and subcutaneous adipose tissue area (P = 0.016).

Conclusions:It appears likely that ESR1 contributes to T2DM and cardiovascular disease risk via pleiotropic effects leading to insulin resistance, a poor lipid profile, and obesity.

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