Bengtsson K, Orho-Melander M, Melander O, Lindblad U, Ranstam J, Råstam L, Groop L
Department of Endocrinology, Malmö University Hospital, Lund University, Malmö, Sweden.
Hypertension. 2001 May;37(5):1303-8. doi: 10.1161/01.hyp.37.5.1303.
The aim of this study was to investigate whether polymorphisms in the beta(2)-adrenergic receptor gene (5'LC-Arg19Cys, Arg16Gly, Gln27Glu) are associated 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 hypertensive patients with type 2 diabetes, and 265 healthy control subjects from SWEDEN: In addition, normotensive sib pairs that were discordant for the Arg16Gly (72 pairs) and Gln27Glu (40 pairs) polymorphisms were identified in type 2 diabetes families from FINLAND: Genotyping was performed using polymerase chain reaction-restriction fragment-length polymorphism analysis. Homozygous carriers of the Arg16 allele had a significantly increased odds ratio (OR) for hypertension in patients with type 2 diabetes (OR 2.14; 95% confidence 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 showed a weaker association to hypertension (OR 1.55; 95% CI, 1.00 to 2.41) and 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 siblings homozygous for the Gly16 allele. These results indicate that the Arg16 allele of the beta(2)-adrenergic receptor gene confers an increased risk 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 are discordant for the polymorphism.
本研究旨在调查β₂-肾上腺素能受体基因多态性（5'LC-Arg19Cys、Arg16Gly、Gln27Glu）是否与2型糖尿病患者或非2型糖尿病患者的高血压相关，以及与血压正常的同胞对中的血压水平相关。关联研究纳入了291例无2型糖尿病的高血压患者、124例有2型糖尿病的高血压患者以及来自瑞典的265例健康对照者：此外，在来自芬兰的2型糖尿病家族中鉴定出了Arg16Gly（72对）和Gln27Glu（40对）多态性不一致的血压正常的同胞对：采用聚合酶链反应-限制性片段长度多态性分析进行基因分型。在2型糖尿病患者中，Arg16等位基因的纯合携带者患高血压的优势比（OR）显著增加（OR 2.14；95%置信区间[CI]，1.05至4.33），尤其是在瘦（体重指数<27 kg/m²）患者中（OR 3.47；95%CI，1.06至11.33）。Gln27等位基因与高血压的关联较弱（OR 1.55；95%CI，1.00至2.41），并且发现其与5'LC-Arg19Cys多态性的Cys19等位基因处于连锁不平衡状态。在同胞配对分析中，至少有1个Arg16等位基因拷贝的同胞收缩压较高（P = 0.049），且非糖尿病同胞的体重指数高于Gly16等位基因纯合的同胞（P = 0.026）。这些结果表明，β₂-肾上腺素能受体基因的Arg16等位基因使2型糖尿病患者患高血压的风险增加，并且与该多态性不一致的同胞对中较高的血压水平和较高的体重指数相关。
