Association Between Genetic Variation in the SCN10A Gene and Cardiac Conduction Abnormalities in Patients With Hypertrophic Cardiomyopathy
Association Between Genetic Variation in the SCN10A Gene and Cardiac Conduction Abnormalities in Patients With Hypertrophic Cardiomyopathy
复制标题
DOI：
10.1536/ihj.14-411
复制
发表时间：
2015-07-01
影响因子：
1.5
通讯作者：
Higaki, Jitsuo
中科院分区：
文献类型：
--
作者：
Iio, Chiharuko;Ogimoto, Akiyoshi;Higaki, Jitsuo
在肥厚型心肌病(HCM)患者中，心律失常与生活质量下降和预后不良有关。最近的全基因组关联研究表明，SCN10A基因中的非同义单核苷酸多态rs6795970与PR区间相关。我们检测了SCN10A基因中PR延长等位基因(A等位基因)是否与肥厚性心肌病患者的心脏传导异常相关，并对149例肥厚性心肌病患者进行了基因分型。传导异常定义为一度心传导阻滞、束支传导阻滞和双束支传导阻滞。将患者分为两组：A组122例(82%)无传导异常，B组27例(18%)有一种或多种心脏传导异常。SCN10A基因(G/G、G/A和A/A)在肥厚性心肌病患者中的分布频率分别为71%、26%和3%。GIG组心脏传导异常发生率为9%，G/A或A/A组为40%，两组比较差异有统计学意义(P=0.0002)。在显性A等位基因模型中，两组间存在显著差异(P<；0.0001)。此外，在多变量模型中调整其他协变量后，A等位基因仍然显著(优势比=6.3[95%可信区间：2.24~19.09]，P=0.0005)。SCN10A基因中的rs6795970可能与心肌梗死患者的心脏传导异常有关，据报道，SCN10A基因存在心脏传导障碍的高风险。
Arrhythmias are associated with reduced quality of life and poor prognosis in patients with hypertrophic cardiomyopathy (HCM). Recent genome-wide association studies revealed that a nonsynonymous single nucleotide polymorphism, rs6795970, in the SCN10A gene was associated with the PR interval. We examined whether the PR prolonging allele (A allele) in the SCN10A gene may be associated with cardiac conduction abnormalities in HCM patients.We genotyped the polymorphism in 149 HCM patients. Conduction abnormalities were defined as first-degree heart block, bundle-branch block, and bifascicular heart block. Patients were divided into two groups: group A consisted of 122 patients (82%) without a conduction abnormality; and group B consisted of 27 patients (18%) with one or more cardiac conduction abnormalities. The frequency distribution of the SCN10A genotypes (G/G, G/A, and A/A) among the patients with HCM was 71%, 26%, and 3%, respectively. A cardiac conduction abnormality was documented in 9% with GIG and 40% with G/A or A/A. There was a significant difference in the genotype distribution between the two groups (P = 0.0002). In the dominant A allele model, there was a significant difference in genotypes between the two groups (P < 0.0001). In addition, the A allele remained significant after adjusting for other covariates in a multivariate model (odds ratio = 6.30 [95% confidence interval: 2.24 to 19.09], P = 0.0005).The rs6795970 in the SCN10A gene, which is reported to carry a high risk of heart block, might be associated with cardiac conduction abnormalities in HCM patients.