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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Acknowledgements Support for this work was provided by National Heart, Lung, and Blood Institute contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, and N01-HC-55022. Dr. Brancati was supported by an Established Investigator Grant from the American Heart Association (Dallas, Tex.). The authors wish to acknowledge the valuable contribution made by the ARIC staff at the following collaborating institutions: The University of North Carolina at Chapel Hill; The University of North Carolina, Forsyth County; The Wake Forest University, North Carolina; The University of Mississippi Medical Center, Jackson; The University of Minnesota, Minneapolis; The Johns Hopkins University, Baltimore; The University of Texas, Houston.