Genetic variation in the α 1A-adrenergic receptor and phenylephrine-mediated venoconstriction

A. Adefurin, L. V. Ghimire, U. Kohli, M. Muszkat, G. G. Sofowora, C. Li, S. Y. Paranjape, C. M. Stein, D. Kurnik*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

There is large interindividual variability and ethnic differences in phenylephrine-mediated vasoconstriction. We tested the hypothesis that genetic variation in ADRA1A, the α 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 ED 50 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 logED 50 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.

Original languageAmerican English
Pages (from-to)310-315
Number of pages6
JournalPharmacogenomics Journal
Volume15
Issue number4
DOIs
StatePublished - 25 Aug 2015
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by Vanderbilt CTSA grant 1 UL1 TR000445 from the National Center for Research Resources and P01 HL56693 from the National Institutes of Health. CMS is the recipient of the Dan May Chair in Medicine.

Publisher Copyright:
© 2015 Macmillan Publishers Limited.

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