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(Circulation. 2001;104:187.)
© 2001 American Heart Association, Inc.

Clinical Investigation and Reports

Polymorphism in the ß₁-Adrenergic Receptor Gene and Hypertension

Kristina Bengtsson, MD; Olle Melander, MD, PhD; Marju Orho-Melander, PhD; Ulf Lindblad, MD, PhD; Jonas Ranstam, PhD; Lennart Råstam, MD, PhD; Leif Groop, MD, PhD

From the Departments of Endocrinology (K.B., O.M., M.O.-M., L.G.) and Community Medicine (U.L., L.R.), Malmö University Hospital, Lund University; Billingen Health Care Center Skövde (K.B.) and Skaraborg Institute, Skövde (U.L.); and Malmö University (J.R.), Malmö, Sweden.

Reprint requests and correspondence to K. Bengtsson, MD, Billingen Health Care Center, Ekängsvägen 15, S-541 40 Skövde, Sweden. E-mail kristina.a.bengtsson{at}vgregion.se

Background—— The Arg389 variant of the ß₁-adrenergic receptor gene mediates a higher isoproterenol-stimulated adenylate cyclase activity than the Gly389 variant in vitro. We investigated whether the Arg389Gly or the Ser49Gly polymorphism is associated with hypertension in Scandinavians.

Methods and Results—— A total of 292 unrelated, nondiabetic, hypertensive patients and 265 unrelated healthy control subjects were included in a case-control association study. From 118 families, 102 nondiabetic sibling pairs without antihypertensive medication who were discordant for the Arg389Gly polymorphism were selected for a sibling study. Allele and genotype frequencies of the Arg389Gly and Ser49Gly polymorphisms were compared between hypertensive patients and normotensive control subjects. Blood pressure and heart rate were compared between carriers of the different genotypes. In the case-control study, the age- and body mass index-adjusted odds ratio for hypertension in subjects homozygous for the Arg389 allele was 1.9 (95% confidence interval, 1.3 to 2.7; P=0.0005) when compared with carriers of 1 or 2 copies of the Gly389 allele. The genotype-discordant sibling pair analysis revealed that siblings homozygous for the Arg389 allele had significantly higher diastolic blood pressures (79.4±9.9 versus 76.0±10.1 mm Hg; P=0.003) and higher heart rates (68.3±11.0 versus 65.1±9.4 bpm; P=0.02) than siblings carrying 1 or 2 copies of the Gly389 allele. The Ser49Gly polymorphism was not associated with hypertension.

Conclusion—— Our data suggest that individuals homozygous for the Arg389 allele of the ß₁-adrenergic receptor gene are at increased risk to develop hypertension.

Key Words: genetics • hypertension • receptors, adrenergic, beta

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