Higher cardiorespiratory fitness attenuates the risk of atherosclerosis associated with ADRB3 Trp64Arg polymorphism

beta 3-Adrenergic receptor (ADRB3) Trp64Arg polymorphism is associated with atherogenic risk factors that include weight gain, insulin resistance, and diabetes. Habitual exercise brings higher cardiorespiratory fitness and results in the amelioration of atherosclerotic risk factors. However, the effects of cardiorespiratory fitness level and ADRB3 Trp64Arg polymorphism on the risk of cardiovascular disease remain unclear. A cross-sectional investigation of 877 Japanese men and women (18-75 years old) was performed to clarify the effects of cardiorespiratory fitness on the relationship between ADRB3 Trp64Arg polymorphism and risk of cardiovascular disease. Common carotid intima-media thickness (ccIMT) and blood lipid profiles were assessed as surrogate markers of atherosclerosis. We measured peak oxygen uptake (O-2peak) during incremental cycle ergometer exercise testing. Subjects were divided into groups with high (High-Fit) and low (Low-Fit) levels of cardiorespiratory fitness based on the median value of O-2peak for sex and decade. Levels of body fat, triglycerides, and plasma glucose were lower and high-density lipoprotein cholesterol levels and O-2peak were higher in High-Fit subjects than Low-Fit subjects. ADRB3 Trp64Arg polymorphism did not significantly affect ccIMT or blood lipid profiles. In Low-Fit subjects, ccIMT was higher in individuals with the Arg/Arg genotype compared to the Trp/Trp and Trp/Arg genotypes (each P < 0.0001); however, ADRB3 polymorphism had no effect in High-Fit subjects. Higher levels of cardiorespiratory fitness may attenuate the risk of atherosclerosis associated with ADRB3 Trp64Arg polymorphism.