title: 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.
abstract: 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.
  
  
  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.affiliation: Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Carla J
authors.initials: CJ
authors.lastname: Gallagher
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: Candace J
authors.initials: CJ
authors.lastname: Gordon
authors.forename: Joel K
authors.initials: JK
authors.lastname: Campbell
authors.forename: Josyf C
authors.initials: JC
authors.lastname: Mychaleckyj
authors.forename: Josyf C
authors.initials: JC
authors.lastname: Mychalecky
authors.forename: Michael
authors.initials: M
authors.lastname: Bryer-Ash
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.forename: Donald W
authors.initials: DW
authors.lastname: Bowden
authors.forename: Michèle M
authors.initials: MM
authors.lastname: Sale
mesh_terms: D050154:Adiposity; D000328:Adult; D001741:Black or African American / Q000208:ethnology / Q000235:genetics*; D050197:Atherosclerosis / Q000150:complications / Q000208:ethnology / Q000235:genetics* / Q000473:pathology*; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics / Q000473:pathology; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance / Q000208:ethnology / Q000235:genetics*; D007438:Introns / Q000235:genetics; D050356:Lipid Metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000208:ethnology / Q000235:genetics* / Q000473:pathology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D047628:Estrogen Receptor alpha; D005947:Glucose