Association of Hypertension with β 2 - and α 2c10 -Adrenergic Receptor Genotype

Abstract

The adrenergic receptors have been implicated in the pathogenesis of essential hypertension. We hypothesized that hypertension is associated with variants at the β ₂ -adrenergic receptor locus and at one of the α ₂ -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 β ₂ - and α _2c10 -adrenergic receptor restriction fragment length polymorphisms. In 175 subjects (49% with hypertension, 55% black), both hypertension and race were associated with genotype at the β ₂ locus (χ ² for hypertension=11, P =.004; χ ² for race=8.8, P =.012). The association with hypertension persisted in each race group separately (blacks only: χ ² =9.6, P =.008; whites only: χ ² =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 β ₂ -adrenergic receptor gene is a candidate gene for hypertension in blacks and whites. We also genotyped subjects at the α ₂ -adrenergic receptor coded on chromosome 10. There was no association between hypertension and genotype at the α _2c10 locus in the total group or in blacks, but there was significant association in whites (χ ² =6.7, P =.03). These data suggest that the β ₂ - and α _2c10 -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.