The β3-adrenergic receptor (β3-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 β3-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 β3-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 intima-media 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 β3-AR Trp64Arg polymorphism is not a major predictor of atherosclerosis or incident CHD in this sample of middle-aged white Americans.
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