beta(2)-adrenergic receptor gene variation and hypertension in subjects with type 2 diabetes

The aim of this study was to investigate whether polymorphisms in the beta (2)-adrenergic receptor gene (5'LC-Arg19Cys, Arg16Gly, Gln27Glu) are associ ated with hypertension in patients with or without type 2 diabetes and with the blood pressure levels in normotensive sib pairs. The association study included 291 hypertensive patients without type 2 diabetes, 124 hypertensi ve patients with type 2 diabetes, and 265 healthy control subjects from Swe den. In addition, normotensive sib pairs that were discordant for the Arg16 Gly (72 pairs) and Gln27Glu (40 pairs) polymorphisms were identified in typ e 2 diabetes families from Finland. Genotyping was performed using polymera se chain reaction-restriction fragment-length polymorphism analysis. Homozy gous carriers of the Arg16 allele had a significantly increased odds ratio (OR) for hypertension in patients with type 2 diabetes (OR 2.14; 95% confid ence interval [CI], 1.05 to 4.33) particularly among lean (body mass index< 27 kg/m(2)) patients (OR 3.47; 95% CI, 1.06 to 11.33). The Gln27 allele sho wed a weaker association to hypertension (OR 1.55; 95% CI, 1.00 to 2.41) an d was found to be in linkage disequilibrium with the Cys19 allele of the 5' LC-Arg19Cys polymorphism. In the paired-sibling analysis, siblings with at least 1 copy of the Arg16 allele had higher systolic blood pressure(P=0.049 ), and nondiabetic siblings had a higher body mass index (P=0.026) than sib lings homozygous for the Gly16 allele. These results indicate that the Arg1 6 allele of the <beta>(2)-adrenergic receptor gene confers an increased ris k for hypertension in subjects with type 2 diabetes and is associated with higher blood pressure levels and higher body mass index in sib pairs who ar e discordant for the polymorphism.