Stangl K, Cascorbi I, Laule M, Stangl V, Meisel C, Wernecke K D, Ziemer S, Baumann G, Roots I, Hauner H
Medizinische Klinik und Poliklinik, Institut für Klinische Pharmakologie, Deutsches Diabetes Forschungsinstitut an der Heinrich Heine, Universität Düsseldorf, Germany.
Metabolism. 2001 Feb;50(2):184-8. doi: 10.1053/meta.2001.20179.
There is some evidence that the Trp64Arg polymorphism of the beta3-adrenergic receptor (beta3-AR) is associated with atherogenic risk factors that include weight gain, insulin resistance, and diabetes. The objective of this cross-sectional study was to investigate the relationship between the Trp64Arg polymorphism and coronary artery disease (CAD). A total of 1,000 consecutive patients with angiographically confirmed CAD and 1,000 controls, carefully matched for age and sex, were genotyped for the Trp64Arg polymorphism by polymerase chain restriction and subsequent restriction fragment length polymorphism analysis. Among cases with CAD, 83.3% were wild-type Trp/Trp, 15.8% were heterozygotes, and 0.9% were homozygous Arg/Arg compared with 82.3%, 17.3%, and 0.4%, respectively, among controls (P = .27). The odds ratios for the presence of Trp/Arg and Arg/Arg in cases and controls were 0.90 (95% confidence interval [CI] 0.7 to 1.2; P = .40) and 2.2 (95% CI 0.7 to 7.2; P = .17), respectively. There was no effect modification by gender and atherogenic risk factors, including diabetes, hypercholesterolemia, hypertension, and smoking. Furthermore, there was no evidence of an association with premature disease onset (< 40 years) or extent of disease. In conclusion, the results of this study in a large sample of clinically well-characterized patients indicate that neither the Trp/Arg nor the Arg/Arg genotype represents a major risk factor for angiographically confirmed coronary artery disease.
有证据表明,β3-肾上腺素能受体(β3-AR)的色氨酸64位精氨酸(Trp64Arg)多态性与包括体重增加、胰岛素抵抗和糖尿病在内的动脉粥样硬化危险因素相关。这项横断面研究的目的是调查Trp64Arg多态性与冠状动脉疾病(CAD)之间的关系。通过聚合酶链反应限制性片段长度多态性分析,对1000例经血管造影证实患有CAD的连续患者和1000例年龄和性别匹配的对照进行Trp64Arg多态性基因分型。在CAD患者中,83.3%为野生型Trp/Trp,15.8%为杂合子,0.9%为纯合子Arg/Arg;而在对照组中,相应比例分别为82.3%、17.3%和0.4%(P = 0.27)。病例组和对照组中Trp/Arg和Arg/Arg基因型的比值比分别为0.90(95%置信区间[CI] 0.7至1.2;P = 0.40)和2.2(95%CI 0.7至7.2;P = 0.17)。性别和包括糖尿病、高胆固醇血症、高血压和吸烟在内的动脉粥样硬化危险因素对结果没有影响。此外,没有证据表明该多态性与疾病过早发作(<40岁)或疾病程度有关。总之,这项对大量临床特征明确的患者样本进行的研究结果表明,Trp/Arg和Arg/Arg基因型均不是血管造影证实的冠状动脉疾病的主要危险因素。