Genetic variation in the alpha_1B-adrenergic receptor and vascular response

The alpha 1B (α 1B)-adrenergic receptors contribute to vasoconstriction in humans. We tested the hypothesis that variation in the ADRA1B gene contributes to interindividual variability and ethnic differences in adrenergic vasoconstriction. We measured dorsal hand vein responses to increasing doses of phenylephrine in 64 Caucasians and 41 African Americans and genotyped 34 ADRA1B variants. We validated findings in another model of catecholamine-induced vasoconstriction, the increase in mean arterial pressure ("MAP) during a cold pressor test (CPT). One ADRA1B variant, rs10070745, present in 14 African-American heterozygotes but not in Caucasians, was associated with a lower phenylephrine ED 50 (geometric mean (95% confidence interval), 144 (69-299) ng ml 1) compared with 27 African-American non-carriers (208 (130-334) ng ml 1; P=0.015) and contributed to the ethnic differences in ED 50. The same variant was also associated with a greater "MAP during CPT (P=0.008). In conclusion, ADRA1B rs10070745 was significantly associated with vasoconstrictor responses after adrenergic stimulation and contributed to the ethnic difference in phenylephrine sensitivity.