Polymorphism in the beta(1)-adrenergic receptor gene and hypertension

Background-The Arg389 variant of the beta (1)-adrenergic receptor gene medi ates a higher isoproterenol-stimulated adenylate cyclase activity than the Gly389 variant in vitro. We investigated whether the Arg389Gly or the Ser49 Gly polymorphism is associated with hypertension in Scandinavians. Methods and Results-A total of 292 unrelated, nondiabetic, hypertensive pat ients and 265 unrelated healthy control subjects were included in a case-co ntrol association study. From 118 families, 102 nondiabetic sibling pairs w ithout antihypertensive medication who were discordant for the Arg389Gly po lymorphism were selected for a sibling study. Allele and genotype frequenci es of the Arg389Gly and Ser49Gly polymorphisms were compared between hypert ensive patients and normotensive control subjects. Blood pressure and heart rate were compared between carriers of the different genotypes, In the cas e-control study, the age- and body mass index-adjusted odds ratio for hyper tension in subjects homozygous for the Arg389 allele was 1.9 (95% confidenc e interval, 1.3 to 2.7; P=0.0005) when compared with carriers of 1 or 2 cop ies of the Gly389 allele. The genotype-discordant sibling pair analysis rev ealed that siblings homozygous for the Arg389 allele had significantly high er diastolic blood pressures (79.4 +/-9.9 versus 76.0 +/- 10.1 mm Hg; P=0.0 03) and higher heart rates (68.3 +/- 11.0 versus 65.1 +/-9.4 bpm; P=0.02) t han siblings carrying 1 or 2 copies of the Gly389 allele. The Ser49Gly poly morphism was not associated with hypertension. Conclusion-Our data suggest that individuals homozygous for the Arg389 alle le of the beta (1)-adrenergic receptor gene are at increased risk to develo p hypertension.