title: 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.
authors.affiliation: Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: A
authors.initials: A
authors.lastname: Adefurin
authors.affiliation: Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: L V
authors.initials: LV
authors.lastname: Ghimire
authors.affiliation: Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: U
authors.initials: U
authors.lastname: Kohli
authors.affiliation: Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: M
authors.initials: M
authors.lastname: Muszkat
authors.affiliation: Division of Clinical Pharmacology, Departments of Medicine and 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: Vanderbilt Genetics Institute, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: R T
authors.initials: RT
authors.lastname: Levinson
authors.affiliation: Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: S Y
authors.initials: SY
authors.lastname: Paranjape
authors.affiliation: Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Stein
authors.affiliation: Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA.|Clinical Pharmacology Unit, Rambam Medical Center, Haifa, Israel.|Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: D
authors.initials: D
authors.lastname: Kurnik
mesh_terms: D000328:Adult; D044383:Black People / Q000235:genetics; D002395:Catecholamines / Q000494:pharmacology; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics*; D014661:Vasoconstriction / Q000235:genetics*; D014680:Veins / Q000187:drug effects; D044465:White People / Q000235:genetics; D001741:Black or African American
chemical_list: C547716:ADRA1B protein, human; D002395:Catecholamines; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine