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.
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.
Authors: Sue K Park; Gabriella Andreotti; Asif Rashid; Jinbo Chen; Philip S Rosenberg; Kai Yu; Jennifer Olsen; Yu-Tang Gao; Jie Deng; Lori C Sakoda; Mingdong Zhang; Ming-Chang Shen; Bing-Sheng Wang; Tian-Quan Han; Bai-He Zhang; Meredith Yeager; Stephen J Chanock; Ann W Hsing Journal: Carcinogenesis Date: 2010-02-19 Impact factor: 4.944
Authors: Kathy L E Klos; Eric Boerwinkle; Robert E Ferrell; Stephen T Turner; Alanna C Morrison Journal: J Lipid Res Date: 2008-04-30 Impact factor: 5.922
Authors: Tennille S Leak; Josyf C Mychaleckyj; Shelly G Smith; Keith L Keene; Candace J Gordon; Pamela J Hicks; Barry I Freedman; Donald W Bowden; Michèle M Sale Journal: Hum Genet Date: 2008-06-17 Impact factor: 4.132
Authors: Yan Chen; Xiao-yan Jiang; Li Xu; Xia Li; Fei-fei Cao; Lei Li; Ming Lu; Li Jin; Xiao-feng Wang Journal: Lipids Date: 2009-07-04 Impact factor: 1.880