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

The Pharmacogenomics Journal volume 15, pages 310–315 (2015)Cite this article

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Abstract

There is large interindividual variability and ethnic differences in phenylephrine-mediated vasoconstriction. We tested the hypothesis that genetic variation in ADRA1A, the α1A 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 Emax ranged from 13.5–100%. The rs574647 variant was associated with a trend towards lower logED50 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.

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Acknowledgements

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.

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Author notes

  1. A Adefurin and L V Ghimire: These authors contributed equally to this work.

Authors and Affiliations

  1. Departments of Medicine and Pharmacology, Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA

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

  2. Department of Biostatistics, Center for Human Genetics Research, Vanderbilt University School of Medicine, Nashville, TN, USA

    C Li

  3. Clinical Pharmacology Unit, Section of Clinical Pharmacology and Toxicology, Rambam Health Care Campus, Haifa, Israel

    D Kurnik

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  1. A Adefurin
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Correspondence to D Kurnik.

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Adefurin, A., Ghimire, L., Kohli, U. et al. Genetic variation in the α1A-adrenergic receptor and phenylephrine-mediated venoconstriction. Pharmacogenomics J 15, 310–315 (2015). https://doi.org/10.1038/tpj.2014.69

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