Association of hypertension with beta2- and alpha2c10-adrenergic receptor genotype

The adrenergic receptors have been implicated in the pathogenesis of essential hypertension. We hypothesized that hypertension is associated with variants at the beta2-adrenergic receptor locus and at one of the alpha2-adrenergic receptor loci. In unrelated individuals, we measured untreated blood pressure and characterized each subject as hypertensive or normotensive. We then used genomic DNA to identify beta2- and alpha2c10-adrenergic receptor restriction fragment length polymorphisms. In 175 subjects (49 percent with hypertension, 55 percent black), both hypertension and race were associated with genotype at the beta2 locus (chi2 for hypertension = 11, P = .004, chi2 for race = 8.8, P = .012). The association with hypertension persisted in each race group separately (blacks only: chi2 = 9.6, P = .008; whites only; chi2 = 14.2, P = .001). This association persisted in a logistic model that controlled for race (P = .01). Genotype was also significantly associated with baseline systolic, diastolic, and mean arterial blood pressures (P = .05, .01, and .02, respectively). These data suggest that the beta2-adrenergic receptor gene is a candidate gene for hypertension in blacks and whites. We also genotyped subjects at the alpha2-adrenergic receptor coded on chromosome 10. There was no association between hypertension and genotype at the alpah2c10 locus in the total group or in blacks, but there was significant association in whites (chi2 = 6.7, P = .03). These data suggest that the beta2- and alph2c10-adrenergic receptor genes may contribute, in a race-specific manner, to the inheritance of essential hypertension. Linkage studies in related individuals are needed to confirm these findings.