Trp64Arg mutation of beta3-adrenergic receptor in essential hypertension: insulin resistance and the adrenergic system.

A putative pathogenic mutation in the beta3-adrenergic receptor gene (Trp64Arg) has been reported to be associated with higher diastolic blood pressure as well as clinical features of the insulin resistance syndrome and an earlier onset of non-insulin-dependent diabetes mellitus (NIDDM) in Pima Indians and Finns. Because essential hypertension is reported to be associated with insulin resistance, we studied the mutation in Japanese patients with essential hypertension to clarify associations of this mutation with hypertension, insulin resistance, and basal adrenergic state in hypertensive subjects. The allele frequency of the mutation (Arg) in patients with essential hypertension was similar to that in control subjects (35 of 202 alleles [17.3%] v 27 of 146 [18.5%], respectively, P > .7). Insulin sensitivity measured by hyperinsulinemic euglycemic glucose clamp and plasma norepinephrine and epinephrine levels were also similar in hypertensive subjects with and without the mutation. These data suggest that Trp64Arg mutation in the beta3-adrenergic receptor gene does not play a major role in susceptibility to essential hypertension or in insulin resistance and basal adrenergic state in hypertension.