ESSENTIAL-HYPERTENSION IN AFRICAN CARIBBEAN ASSOCIATES WITH A VARIANTOF THE BETA(2)-ADRENOCEPTOR

Populations of West African ancestry dwelling in Western communities e xhibit greater prevalence of human essential hypertension and higher r ates of end-organ damage. The sympathetic nervous system influences ca rdiac output, vascular tone, renal sodium reabsorption, and renin rele ase and could be implicated in enhanced vascular responsiveness observ ed in African hypertensives. Such an effect could arise from genetic v ariants that alter agonist response of alpha-adrenoceptors, leading to enhanced vasoconstriction, or attenuate beta(2)-adrenoceptor-mediated vasodilatation. Indeed, there is evidence of a blunted vasodilator re sponse to the beta-agonist isoprenaline in African Americans. A varian t of the beta(2)-adrenoceptor gene that encodes glycine rather than ar ginine at position 16 (Arg16-->Gly) has been shown to confer exaggerat ed agonist mediated receptor downregulation, which might attenuate vas odilator 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 Argl6 alleles by using an allele-specific polymerase chain reaction method. We repo rt strong support for association of the prodownregulatory glycine 16 variant of the beta(2)-adrenoceptor gene with hypertension in African Caribbeans from SI Vincent and the Grenadines (chi(2) = 18.9, P = .000 014, 1 df). This observation, coupled with reports of attenuated vasod ilator responses to beta-agonists among people of West African ancestr y, may provide a mechanism for enhanced vascular reactivity and identi fy a candidate gene for hypertension in this ethnic group.