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.
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.
Gallagher
Carla J
CJ
Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Langefeld
Carl D
CD
Gordon
Candace J
CJ
Campbell
Joel K
JK
Mychaleckyj
Josyf C
JC
Mychalecky
Josyf C
JC
Bryer-Ash
Michael
M
Rich
Stephen S
SS
Bowden
Donald W
DW
Sale
Michèle M
MM
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
D047628:Estrogen Receptor alpha; D005947:Glucose