Essential Hypertension in African Caribbeans Associates With a Variant of the β 2 -Adrenoceptor

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 1997-10, Vol.30 (4), p.773-776
• Main Authors: Kotanko, Peter, Binder, Alexander, Tasker, Jacquie, DeFreitas, Perry, Kamdar, Sejal, Clark, Adrian J. L., Skrabal, Falko, Caulfield, Mark
• Format: Article
• Language: English
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.HYP.30.4.773

Abstract Populations of West African ancestry dwelling in Western communities exhibit greater prevalence of human essential hypertension and higher rates of end-organ damage. The sympathetic nervous system influences cardiac output, vascular tone, renal sodium reabsorption, and renin release and could be implicated in enhanced vascular responsiveness observed in African hypertensives. Such an effect could arise from genetic variants that alter agonist response of α-adrenoceptors, leading to enhanced vasoconstriction, or attenuate β 2 -adrenoceptor–mediated vasodilatation. Indeed, there is evidence of a blunted vasodilator response to the β-agonist isoprenaline in African Americans. A variant of the β 2 -adrenoceptor gene that encodes glycine rather than arginine at position 16 (Arg16→Gly) has been shown to confer exaggerated agonist-mediated receptor downregulation, which might attenuate vasodilator response. One hundred thirty-six unrelated hypertensives and 81 unrelated normotensives of African Caribbean origin were identified from primary care on the island of St Vincent. Genomic DNA from these subjects was analyzed for the presence of the Gly16 and Arg16 alleles by using an allele-specific polymerase chain reaction method. We report strong support for association of the prodownregulatory glycine 16 variant of the β 2 -adrenoceptor gene with hypertension in African Caribbeans from St Vincent and the Grenadines (χ 2 =18.9, P =.000014, 1 df ). This observation, coupled with reports of attenuated vasodilator responses to β-agonists among people of West African ancestry, may provide a mechanism for enhanced vascular reactivity and identify a candidate gene for hypertension in this ethnic group.