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β2-肾上腺素能受体基因变异 Arg16Gly 与特发性室性流出道心动过速有关。

Beta2-adrenoceptor gene variant Arg16Gly is associated with idiopathic ventricular outflow-tract tachycardia.

机构信息

Center for Arrhythmia Diagnosis and Treatment, Fu Wai Cardiovascular Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100037, China.

出版信息

Chin Med J (Engl). 2010 Sep;123(17):2299-304.

PMID:21034538
Abstract

BACKGROUND

Imbalance of the sympathetic nervous system was involved in the pathogenesis of idiopathic ventricular outflow-tract tachycardia (IVOT). We aimed to investigate whether the major genetic variants in β(1)- and β(2)-adrenoceptors and GNB3 C825T were associated with IVOT and verapamil sensitive idiopathic left ventricular tachycardia (ILVT).

METHODS

Patients with IVOT and ILVT from December 2005 to December 2007 were consecutively enrolled into this study. Controls were randomly selected from the community-based inhabitants. Five genetic variants, Ser49Gly and Gly389Arg in the β(1)-adrenoceptor, Arg16Gly and Gln27Glu in the β(2)-adrenoceptor and GNB3 C825T, were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis.

RESULTS

A total of 227 patients with IVOT and 110 patients with ILVT were included. Genotyping revealed that the 16Gly allele of Arg16Gly variant of β(2)-adrenoceptor was associated with a higher risk of IVOT (OR: 1.40, 95%CI: 1.12 - 1.75, P = 0.003 in the addictive model and OR: 1.62, 95%CI: 1.14 - 2.31, P = 0.007 in the dominant model). Patients with Gly16Gln27 haplotype also had a higher risk of IVOT (OR: 1.38, 95%CI: 1.11 - 1.73, P = 0.012). Other four variants, including Ser49Gly and Arg389Gly in β(1)-adrenoceptor, Gln27Glu in β(2)-adrenoceptor and GNB3 C825T, did not differ between patients with IVOT and controls. In patients with ILVT, no significant difference was found in these five variants compared with controls.

CONCLUSIONS

Arg16Gly in β(2)-adrenoceptor is significantly associated with IVOT in Chinese Han population. Major genetic variants in β(1)- and β(2)-adrenoceptor and GNB3 C825T may not be associated with ILVT. These data suggest a different arrhythmogenic mechanism in IVOT and ILVT.

摘要

背景

交感神经系统失衡与特发性室流出道心动过速(IVOT)的发病机制有关。我们旨在研究β(1)-和β(2)-肾上腺素能受体和 GNB3 C825T 的主要遗传变异是否与 IVOT 和维拉帕米敏感的特发性左室心动过速(ILVT)相关。

方法

2005 年 12 月至 2007 年 12 月,连续入选 IVOT 和 ILVT 患者入组本研究。对照组从社区居民中随机选择。通过聚合酶链反应-限制性片段长度多态性分析对 Ser49Gly 和 Gly389Arg 在内的β(1)-肾上腺素能受体、Arg16Gly 和 Gln27Glu 在β(2)-肾上腺素能受体和 GNB3 C825T 中的 5 个遗传变异进行基因分型。

结果

共纳入 227 例 IVOT 患者和 110 例 ILVT 患者。基因分型显示,β(2)-肾上腺素能受体 Arg16Gly 变异的 16Gly 等位基因与 IVOT 风险增加相关(OR:1.40,95%CI:1.12-1.75,P=0.003 在附加模型中和 OR:1.62,95%CI:1.14-2.31,P=0.007 在显性模型中)。Gly16Gln27 单体型患者也有更高的 IVOT 风险(OR:1.38,95%CI:1.11-1.73,P=0.012)。β(1)-肾上腺素能受体中的 Ser49Gly 和 Arg389Gly 以及β(2)-肾上腺素能受体中的 Gln27Glu 和 GNB3 C825T 等其他四个变异在 IVOT 患者和对照组之间无差异。与对照组相比,ILVT 患者的这五个变异均无显著差异。

结论

中国汉族人群中β(2)-肾上腺素能受体 Arg16Gly 与 IVOT 显著相关。β(1)-和β(2)-肾上腺素能受体和 GNB3 C825T 的主要遗传变异可能与 ILVT 无关。这些数据表明 IVOT 和 ILVT 的心律失常机制不同。

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