Genetic polymorphism of the α2-adrenergic receptor is associated with increased platelet aggregation, baroreceptor sensitivity, and salt excretion in normotensive humans

It is likely that a number of independent heritable traits, each encoded by a singular gene, contribute to pathologic elevations in blood pressure in humans. Genetic polymorphisms of individual genes may result in intermediate phenotypes which, by themselves, do not raise blood pressure, but, coupled with environmental or epistatic forces, contribute to the prevalence of human hypertension. The gene for the α2-adrenergic receptor encoded by chromosome 10 (C10 A2AR) is polymorphic, and Southern blotting with a cDNA probe following restriction enzyme digest of this gene results in fragments of either 6.3 kb or 6.7 kb in size. We reported an association between homozygosity for the 6.3 kb allele and hypertension in blacks. Blacks with hypertension also have an increased risk for thrombotic stroke, increased baroreceptor sensitivity, and decreased sodium excretion. We noted that the C10 A2AR, which modulates norepinephrine release in blood-pressure-regulating regions of the brain, is also expressed on platelets and in the kidney. We postulated that functional changes associated with the C10 A2AR gene polymorphism could be responsible for increased baroreceptor sensitivity, epinephrine-mediated platelet aggregation, and decreased sodium excretion in some individuals. In a study of 81 healthy, college-age, normotensive subjects, we found the following phenotypic differences among those individuals carrying at least one copy of the 6.3 kb allele: 1) increased catecholamine-induced platelet aggregation (differences in optical density due to aggregation induced by 10 µmol/L epinephrine, expressed in arbitrary units ± SEM, 41 ± 5 v 22 ± 4, P < .05); 2) increased heart rate response to lower body negative pressure (mean heart rate increase, expressed as beats/minute ± SEM, 8.7 ± 1.8 v 4.7 ± 1.3, P = .02); and 3) decreased sodium excretion induced by immersion in thermal neutral water (values expressed in mEq/2h ± SEM, 25.6 ± 2.5 v 38.0 ± 3.3, P < .05). Functional polymorphisms of the C10 A2AR may contribute to the increased prevalence of thrombotic stroke, augmented baroreceptor sensitivity, and diminished sodium excretion in some hypertensive individuals, independent of blood pressure Am J Hypertens 1995;8:863–869