Association analysis of β2 adrenoceptor polymorphisms with hypertension in a Black African population


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Abstract

ObjectiveTo determine whether or not β2 adrenoceptor polymorphism is a risk factor for the development of hypertension in a Black South African populationBackgroundAttenuated vasodilator responses to endogenous catecholamines may contribute to the aetiology of hypertension. Downregulation of β2 adrenoreceptors (β2AR) following stimulation with agonists is determined in part by variation at the β2AR gene locus. The Glu27 β2AR genotype results in attenuated downregulation compared with the wild-type Gln27 receptor, whereas Gly16 exhibits enhanced down-regulation compared to Arg16. Possible racial differences in the prevalence of the β2AR polymorphisms may be an explanation for the blunted responses to isoprenaline and the increased prevalence of hypertension in Black African populations.MethodsOne hundred and ninety-two unrelated hypertensives and 123 normotensives of Black South African origin were studied. Hypertensives were recruited from hospital hypertension clinics in the province of Gauteng and if on treatment, had a 2–4 week washout period before 24-h ambulatory blood pressure assessment. Normotensive controls were recruited from the same community.ResultsThere was no significant association between either the Arg–Gly16 polymorphism or the Gln–Glu27 polymorphism and hypertension status. Furthermore, in the hypertensives, no significant association was seen between β2AR genotype at either site and clinical bloodpressure, 24-h blood pressure or left ventricular mass. A significant association was seen between Arg16 homozygotes and lower body mass index in hypertensives (P = 0.007) although this was not a primary end point. Interestingly, the Glu27 polymorphism was much rarer in this population (allelic frequency 17%) compared to a Caucasian population.ConclusionThese data suggest that β2AR polymorphism is not a risk factor for hypertension per se in this defined population. The possibility that the decreased prevalence of Glu27 in black South African populations explains blunted vasodilator responses to isoprenaline requires further study.

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