Association of insulin sensitivity and glucose tolerance with the c.825C>T variant of the G protein beta-3 subunit gene

Abstract The risk of macrovascular complications of diabetes mellitus is greatly enhanced by the presence of high blood pressure. In addition, hypertension and diabetes share insulin resistance as a common pathophysiological mechanism. Despite evidence for a common molecular genetic background of insulin resistance, glucose intolerance, and hypertension, few candidate genes have been shown to influence all of these features simultaneously. We examined the association of insulin sensitivity with the c.825C>T variant of the g-protein beta-3 subunit (GNB3), a candidate gene of hypertension, in families of Mexican-American hypertensive patients. Methods One hundred eighty subjects enrolled in a family study of Mexican-American hypertensive patients were recruited from hypertension clinics in Los Angeles. Subjects underwent pretreatment blood pressure recording, an oral glucose tolerance test, euglycemic hyperinsulinemic clamp, and anthropometric measurements. DNA from peripheral blood leukocytes was genotyped by polymerase chain reaction and restriction enzyme digest with BseD1 (GNB). Statistical analysis was performed by transmission disequilibrium testing. Results In carriers of the T-allele, blood glucose was significantly lower [(mean+S.D.) fasting: 96.7+22.9 vs. 106.7+51.7mg/dl, P =.009; oral glucose tolerance test (oGTT) 120 min: 131.7+48.7 vs. 137.8+64.9 mg/dl, P =.036], and insulin sensitivity was significantly higher (229.0+108.7 vs. 188.5+94.2 mg/kg per minute, P =.037) than in homozygous carriers of the C-allele. Blood pressure did not differ significantly between the phenotypes. Conclusion In a Mexican-American hypertensive population, we found evidence for higher insulin sensitivity in carriers of the T allele of the c.825C>T variant of GNB3.