Functional Variant in the α 2B Adrenoceptor Gene, a Positional Candidate on Chromosome 2, Associates With Hypertension

In a genome-wide scan in Scandinavians, we found suggestive linkage between early-onset primary hypertension and a region on chromosome 2. The alpha(2B)-adrenoceptor gene, a candidate gene within this region, harbors a functional insertion/deletion (I/D) polymorphism of three glutamate residues. The aim of this study was to investigate if the DD genotype is associated with hypertension in Swedes. We performed an association study between the I/D polymorphism of the alpha(2B)-adrenoceptor and hypertension in the Skaraborg population. The material consists of all known patients with primary hypertension in Skara (n=772 nondiabetic subjects; n=171 normoalbuminuric type 2 diabetic subjects) and 817 population control subjects. We first compared genotype frequencies between patients with early-onset hypertension (aged 50 years or younger at onset) and subjects with normotension (blood pressure <120/80 mm Hg). Thereafter, the polymorphism was tested for association with hypertension at the population level. When comparing patients with early-onset hypertension and normotensive subjects, the DD versus II genotype was associated with early-onset hypertension when diabetic subjects were excluded from the analysis (OR=2.0; 95% CI=1.2 to 3.5) or when they were not excluded (OR=1.8; 95% CI=1.0 to 3.1). At the population level, the DD versus II genotype was weakly associated with nondiabetic hypertension (OR=1.4; 95% CI=1.0 to 1.8). Our data suggest that carriers of the DD versus II genotype of the alpha(2B)-adrenoceptor are at increased risk for hypertension. The genotypic effect is most evident when comparing groups corresponding to the upper and lower tails of the blood pressure distribution in the population; however, in nondiabetic hypertensive subjects it is weakly detectable even at the population level.