Genetic variation in the α1A-adrenergic receptor and phenylephrine-mediated venoconstriction

There is large interindividual variability and ethnic differences in phenylephrine-mediated vasoconstriction. We tested the hypothesis that genetic variation in ADRA1A, the alpha(1A) adrenergic receptor gene, contributes to the variability and ethnic differences. We measured local dorsal hand vein responses to increasing doses of phenylephrine in 64 Caucasians and 42 African-Americans and genotyped for 32 ADRA1A single nucleotide polymorphisms. The ED50 ranged from 11 to 5442 ng min(-1), and the E-max ranged from 13.5-100%. The rs574647 variant was associated with a trend towards lower logED(50) in each race and in the combined cohort (P = 0.008). In addition, rs1079078 was associated with a trend to higher logED50 in each race and in the combined cohort (P = 0.011). Neither variant accounted for the ethnic differences in response. None of the ADRA1A haplotypes was associated with the outcomes. In conclusion, ADRA1A variants do not contribute substantially to the marked interindividual variability or ethnic differences in phenylephrine-mediated venoconstriction.