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    Diabetes. 2007 Aug;56(8):2135-41. Epub 2007 May 18.

    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.

    Gallagher CJ, Langefeld CD, Gordon CJ, Campbell JK, Mychaleckyj JC, Bryer-Ash M, Rich SS, Bowden DW, Sale MM.

    Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.

    Erratum in:

    • Diabetes. 2007 Oct;56(10):2650. Mychalecky, Josyf C [corrected to Mychaleckyj, Josyf C].

    OBJECTIVE: 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. 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. 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). 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.

    PMID: 17513703 [PubMed - indexed for MEDLINE]

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