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

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 alpha-adrenoceptors, leading to enhanced vasoconstriction, or attenuate beta2-adrenoceptor-mediated vasodilatation. Indeed, there is evidence of a blunted vasodilator response to the beta-agonist isoprenaline in African Americans. A variant of the beta2-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 beta2-adrenoceptor gene with hypertension in African Caribbeans from St Vincent and the Grenadines (chi2=18.9, P=.000014, 1 df). This observation, coupled with reports of attenuated vasodilator responses to beta-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.

β2 Adrenoceptor Functional Gene Variants, Obesity, and Blood Pressure Level Interactions in the General Population

“…Finally, the 164Ile variant of the ADRB2 is associated with a decreased native adipocyte receptor function. 14 Although several previous reports have described associations between these polymorphisms and hypertension or obesity, [15][16][17][18][19][20] few studies have taken into account both variables in the same design. To our knowledge, this is the most extensive work done analyzing these polymorphisms and blood pressure and obesity phenotypes both as continuous and dichotomous variables in the same population.…”

Genetics of arterial hypertension and hypotension

“…The β2AR polymorphisms accounted for ∼2% of the observed variation in blood pressure (Bray et al 2000). While results of some groups confirmed the association between the 16Gly allele and blood pressure (Kotanko et al 1997;Rosmond et al 2000;Gratze et al 1999), others found opposite effects, i.e., an association between the 16Arg allele and hypertension (Busjahn et al 2000;Bengtsson et al 2001a,b;Timmermann et al 1998) or no effects at all (Herrmann et al 2002;Kato et al 2001;Xie et al 2000; for a recent meta-analysis see Hahntow et al 2006). Again, differing inclusion of haplotypes, variations in ethnicities and different study designs may contribute to these sobering results.…”

?-Amino Acids: Role in Human Biology and Medicinal Chemistry - A Review

“…It was found that the Gly16 allele was more common in hypertensive subjects than in normotensive African-Caribbean controls. Because the Gly16 allele directs an increased propensity for depressed regulation of the receptor, there is a possibility that an impaired vasodilatation in peripheral arteries in response to β 2 AR agonists may play a role in the hypertension of individuals carrying the Gly16 allele [20].…”