title: Alpha1A-adrenergic receptor polymorphism: association with ethnicity but not essential hypertension.
abstract: The alpha1-adrenergic receptor (alpha1-AR) mediates vasoconstriction and plays an important role in the regulation of vascular tone. Increased alpha1-AR-mediated vasoconstrictor sensitivity, increased vascular reactivity to stress, and an increased prevalence of hypertension occur in African-Americans. The human alpha1A-AR is the predominant alpha1-AR subtype in vascular smooth muscle. The potential relevance of alpha1A-AR genetic variation to ethnic differences in vascular response and to the pathogenesis of hypertension prompted us to determine the frequency distribution of a recently identified polymorphism (Arg492 to Cys) in the alpha1A-AR in normotensive and hypertensive black and white American individuals. Polymerase chain reaction-based PstI restriction fragment length polymorphisms in the human alpha1A-AR gene were determined in 231 African-American and 282 Caucasian individuals, both with and without hypertension. There were marked differences in the genotypic and allelic distributions of the Arg492 to Cys alpha1A-AR polymorphism between African-American and Caucasian individuals (Cys492/Cys492 genotype, normotensive: 7.6% versus 30.1%; hypertensive: 7.1% versus 26.2%; Cys492 allele, normotensive: 29.5% versus 53.8%; hypertensive: 28.8% versus 55.2%; blacks versus whites, P < 0.0001). The frequency of the variant Cys492 allele was similar in normotensive and hypertensive individuals, both in African-Americans (29.5% versus 28.8%) and Caucasians (53.8% versus 55.2%). There were no significant intergenotypic differences in blood pressure (all P > 0.05). The data indicate that this polymorphism is not associated with essential hypertension in black or white Americans, but that the frequency of the alpha1A-AR Arg492 allele occurs significantly more commonly in African-Americans than in Caucasians. The potential role of the Arg492 to Cys alpha1A-AR polymorphism in ethnic differences in vascular alpha1-adrenergic response requires further investigation.
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: H G
authors.initials: HG
authors.lastname: Xie
authors.forename: R B
authors.initials: RB
authors.lastname: Kim
authors.forename: C M
authors.initials: CM
authors.lastname: Stein
authors.forename: J V
authors.initials: JV
authors.lastname: Gainer
authors.forename: N J
authors.initials: NJ
authors.lastname: Brown
authors.forename: A J
authors.initials: AJ
authors.lastname: Wood
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D044383:Black People / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics* / Q000502:physiology; D014661:Vasoconstriction; D044465:White People / Q000235:genetics*; D001741:Black or African American
chemical_list: C547713:ADRA1A protein, human; D018340:Receptors, Adrenergic, alpha-1