Genetic variation in the alpha1B-adrenergic receptor and vascular response

Abstract

The alpha1B (α1B)-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 (ΔMAP) 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 ED50 (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 ED50. The same variant was also associated with a greater ΔMAP 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.

Conflict of interest statement

Conflict of Interest: The authors declare no conflict of interest.

Figures

Figure 1

ADRA1B rs10070745 association with sensitivity to phenylephrine (ED50) in African-Americans The columns show geometric means, the error bars the 95% confidence intervals. Carriers of the variant allele had a significantly lower geometric mean ED50 (P=0.015).

Figure 2

Association between rs10070745 and increase in mean arterial pressure (ΔMAP) during the cold pressor test. The columns show the mean, the error bars the standard error of mean. Carriers of the variant alleles had significantly higher mean ΔMAP after CPT (P=0.008).