The codon 64 polymorphism of the beta(3)-adrenergic receptor gene is not associated with coronary heart disease or insulin resistance in nondiabetic subjects and non-insulin-dependent diabetic patients

Hyperinsulinemia has been shown to predict coronary heart disease (CHD) eve nts in both nondiabetic subjects and patients with non-insulin-dependent di abetes mellitus (NIDDM). Therefore, defects in genes that regulate insulin action could be responsible for an increased risk of CHD. The Trp64Arg poly morphism of the beta(3)-adrenergic receptor gene has been linked with abdom inal obesity, insulin resistance, and early-onset NIDDM. Therefore, we scre ened for this polymorphism among 185 unrelated nondiabetic subjects (101 me n and 84 women; age, 56 +/- 1 years [mean +/- SEM]; body mass index [BMI], 27.8 +/- 0.3 kg/m(2)) with angiographically confirmed CHD (stenosis > 50% i n greater than or equal to two coronary arteries), among 119 unrelated pati ents with NIDDM (90 men and 29 women; age, 62 +/- 1 years; BMI, 28.7 +/- 0. 4 kg/m(2); 95 had CHD by the same criteria and 24 had definite myocardial i nfarction [MI]), and among 82 healthy men (age, 54 +/- 1 years; BMI, 26.3 /- 0.4 kg/m(2)) from our previous study. The frequency of the Trp64Arg alle le of the beta(3)-adrenergic receptor gene was similar in nondiabetic patie nts with CHD (8%), NIDDM patients with CHD (7%), and nondiabetic subjects w ithout CHD (7%). No association was found between cardiovascular risk facto rs and the codon 64 polymorphism of the beta(3)-adrenergic receptor gene in patients with CHD. Similarly, this polymorphism was not significantly rela ted to insulin resistance in nondiabetic and NIDDM subjects with CHD evalua ted by the euglycemic clamp technique. These results indicate that the Trp6 4Arg allele of the beta(3)-adrenergic receptor gene does not contribute to the risk of CHD in nondiabetic subjects and NIDDM patients. Copyright (C) 1 999 by W.B. Saunders Company.