title: Genetic variation in the α1A-adrenergic receptor and phenylephrine-mediated venoconstriction.
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.
authors.affiliation: Departments of Medicine and Pharmacology, Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: A
authors.initials: A
authors.lastname: Adefurin
authors.affiliation: Departments of Medicine and Pharmacology, Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: L V
authors.initials: LV
authors.lastname: Ghimire
authors.affiliation: Departments of Medicine and Pharmacology, Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: U
authors.initials: U
authors.lastname: Kohli
authors.affiliation: Departments of Medicine and Pharmacology, Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: M
authors.initials: M
authors.lastname: Muszkat
authors.affiliation: Departments of Medicine and Pharmacology, Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: G G
authors.initials: GG
authors.lastname: Sofowora
authors.affiliation: Department of Biostatistics, Center for Human Genetics Research, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: C
authors.initials: C
authors.lastname: Li
authors.affiliation: Departments of Medicine and Pharmacology, Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: S Y
authors.initials: SY
authors.lastname: Paranjape
authors.affiliation: Departments of Medicine and Pharmacology, Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Stein
authors.affiliation: 1] Departments of Medicine and Pharmacology, Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA [2] Clinical Pharmacology Unit, Section of Clinical Pharmacology and Toxicology, Rambam Health Care Campus, Haifa, Israel.
authors.forename: D
authors.initials: D
authors.lastname: Kurnik
mesh_terms: D000293:Adolescent; D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology*; D000328:Adult; D044383:Black People; D002395:Catecholamines / Q000097:blood; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005006:Ethnicity; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006225:Hand / Q000098:blood supply; D006801:Humans; D008297:Male; D008875:Middle Aged; D010656:Phenylephrine / Q000494:pharmacology*; D020641:Polymorphism, Single Nucleotide; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000235:genetics*; D012039:Regional Blood Flow / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects* / Q000235:genetics*; D044465:White People; D055815:Young Adult; D001741:Black or African American
chemical_list: C547713:ADRA1A protein, human; D058646:Adrenergic alpha-1 Receptor Agonists; D002395:Catecholamines; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine