Essential hypertension in African Caribbeans associates with a variant of the beta2-adrenoceptor.
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.
Kotanko
P
P
Department of Internal Medicine Krankenhaus der Barmherzigen Brüder and Teaching Hospital of the Karl Franzens University Graz, Austria.
Binder
A
A
Tasker
J
J
DeFreitas
P
P
Kamdar
S
S
Clark
A J
AJ
Skrabal
F
F
Caulfield
M
M
D000328:Adult; D000354:Africa, Western / Q000208:ethnology; D000483:Alleles; D044383:Black People / Q000235:genetics*; D001794:Blood Pressure; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011943:Receptors, Adrenergic, beta / Q000235:genetics*; D012016:Reference Values; D014900:West Indies / Q000208:ethnology; D001741:Black or African American
D011943:Receptors, Adrenergic, beta