α1A-Adrenergic receptor polymorphism:: association with ethnicity but not essential hypertension

The alpha(1)-adrenergic receptor (alpha(1)-AR) mediates vasoconstriction and plays an important role in the regulation of vascular tone. Increased alpha(1)-AR-mediated vasoconstrictor sensitivity, increased vascular reactivity to stress, and an increased prevalence of hypertension occur in African-Americans. The human alpha(1A)-AR is the predominant alpha(1)-AR subtype in vascular smooth muscle. The potential relevance of alpha(1A)-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 alpha(1A)-AR in normotensive and hypertensive black: and white American individuals, Polymerase chain reaction-based PstI restriction fragment length polymorphisms in the human alpha(1A)-AR gene were determined in 231 African-American and 282 Caucasian individuals, both with and without hypertension There were marl(ed differences in the genotypic and allelic distributions of the Arg492 to Cys alpha(1A)-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 tall 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 alpha(1A)-AR Arg492 allele occurs significantly more commonly in African-Americans than in Caucasians. The potential role of the Arg492 to Cys alpha(1A)-AR polymorphism in ethnic differences in vascular alpha(1)-adrenergic response requires further investigation. Pharmacogenetics 9:651-656 (C) 1999 Lippincott Williams & Wilkins.