Beta3-adrenergic receptor Trp64Arg polymorphism does not predict incident CHD or carotid intima-media thickness in a community-based sample of whites: the ARIC study. Atherosclerosis Risk in Communities.
The beta3-adrenergic receptor (beta3-AR) is expressed in adipose tissue and plays a significant role in controlling energy expenditure through the regulation of lipolysis and thermogenesis. The possible clinical importance of the beta3-AR Trp64Arg polymorphism has prompted us to investigate the association between it and the extent of atherosclerosis and risk of incident coronary heart disease (CHD). The ability of the beta3-AR Trp64Arg polymorphism to predict the extent of atherosclerosis and incident CHD has been evaluated in participants of the Atherosclerosis Risk in Communities (ARIC) study. Incident CHD cases (n=271) were compared with a stratified random sample of the ARIC cohort (n=700). Comparisons were also made between a group with increased intimamedia thickness (IMT) of the carotid artery walls, but without prevalent CHD (n=324), and a thin-walled control group (n=407). The frequency of the Arg64 allele was 0.081 and 0.069 in the incident CHD cases and cohort sample, respectively, and 0.062 and 0.057 in the IMT cases and thin-walled controls, respectively. Comparison of incident CHD cases and the cohort sample by Cox proportional hazards modeling indicated that the Arg64 allele was not a significant predictor of incident CHD, either alone (RR=0.99, P=0.98) or after inclusion of body mass index (BMI) and fasting insulin and glucose measurements (RR=1.02, P=0.93). A comparison of IMT cases and thin-walled controls by multivariate logistic regression analysis suggested that the Arg64 allele was not a significant predictor of carotid artery intima-media thickness when evaluated alone (OR=1.32, P=0.29) or after BMI and fasting insulin and glucose measurements were added to the model (OR=1.28, P=0.35). We infer that the beta3-AR Trp64Arg polymorphism is not a major predictor of atherosclerosis or incident CHD in this sample of middle-aged white Americans.
Morrison
A C
AC
Human Genetics Center and Institute of Molecular Medicine, University of Texas-Houston Health Science Center, 77030, USA.
Brancati
F L
FL
Folsom
A R
AR
Smith
L
L
Boerwinkle
E
E
D000368:Aged; D000483:Alleles; D019943:Amino Acid Substitution; D001161:Arteriosclerosis / Q000209:etiology / Q000235:genetics / Q000473:pathology; D001483:Base Sequence; D002339:Carotid Arteries / Q000473:pathology*; D015331:Cohort Studies; D003327:Coronary Disease / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D017354:Point Mutation; D011110:Polymorphism, Genetic; D011943:Receptors, Adrenergic, beta / Q000235:genetics*; D022702:Receptors, Adrenergic, beta-3; D012307:Risk Factors; D014481:United States; D044465:White People / Q000235:genetics
D017931:DNA Primers; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3