心房颤动患者KCNQ1、KCNE1和KCNE4基因单核苷酸多态性研究  

The association of single nucleotide polymorphism of slow delayed rectifier K^+ channel genes with atrial fibrillation in Han nationality Chinese

作　　者：曾治宇[1] 浦介麟[1] 谭琛[1] 滕思勇[1] 陈剑虹[2] 宿少勇[2] 周晓阳[2] 张澍[1] 李一石[3] 王方正[1] 顾东风[2] 

机构地区：[1]中国医学科学院中国协和医科大学心血管病研究所阜外心血管病医院心律失常诊治中心 [2]中国医学科学院中国协和医科大学心血管病研究所阜外心血管病医院群体遗传学及防治研究室,北京100037 [3]中国医学科学院中国协和医科大学心血管病研究所阜外心血管病医院临床药理中心,北京100037

出　　处：《中华心血管病杂志》2005年第11期987-991,共5页Chinese Journal of Cardiology

基　　金：国家自然科学基金(30270556)

摘　　要：目的心房颤动(房颤)与缓慢型延迟整流钾离子流(IKS)密切相关,该研究探讨房颤与IKS相关基因KCNQ1、KCNE1及KCNE4单核苷酸多态性(SNP)的相关性。方法采用关联分析,入选汉族对象,房颤病例142例,社区对照120例,病区对照118例。选择亚洲人群特异的非同义SNPKCNQ1P448R、KCNQ1R519H、KCNQ1G643S、KCNE1G38S及KCNE1D85N,对KCNE4基因进行测序,以发现可能存在的SNP。采用限制性内切酶片段长度多态性法确定基因型。结果KCNQ1P448R、KCNQ1R519H、KCNQ1G643S、KCNE1G38S及KCNE1D85N在汉族社区人群中的频率(少见等位基因频率)分别为0·079、0、0·042、0·317、0·004,未证实这些SNP与房颤相关。在KCNE4基因中发现E145D多态,在汉族社区人群中频率高达0·271,LOGISTIC回归分析与房颤显著相关(OR=1·66,P=0·044)。结论KCNQ1P448R、KCNQ1R519H、KCNQ1G643S、KCNE1G38S及KCNE1D85N多态性与房颤无关,KCNE4E145D与房颤有关,其对IKS的功能影响值得进一步研究。Objective To investigate the association between atrial fibrillation and the single nucleotide polymorphism （SNP） of slow delayed rectifier K^＋ channel （IKa） genes in Han nationality Chinese. Methods Three hundred and eighty of Han nationality Chinese （ 142 atrial fibrillation, 120 inhospital and 118 out-hospital control） were enrolled in this study. Asian specific non-synonymous SNPs of KCNQ1 P448R, KCNQ1 R519H, KCNQ1 G643S, KCNE1 G38S and KCNE1 D85N were genotyped by restriction fragment length polymorphism analysis. A newly cloned KCNE4 gene was also screened for any possible SNP. Results The minor allele frequency of KCNQ1 P448R, KCNQ1 R519H, KCNQ1 G643S, KCNE1 G38S and KCNE1 D85N in out-hospital subjects was 0.079, 0, 0.042, 0.317 and 0.004, respectively. None of these SNPs was relationed with any atrial fibrillation phenotype. A KCNE4 E145D was discovered and proven statistically to relation significantly to atrial fibrillation by logistic regression analysis （ OR = 1.66, P = 0. 044）. The minor allele frequency of KCNE4 E145D was as high as 0. 271 in out- hospital subjects. Conclusions None of the SNPs of KCNQ1 P448R, KCNQ1 R519H, KCNQ1 G643S, KCNE1 G38S and KCNE1 D85N was associated with atrial fibrillation phenotype, but KCNE4 E145D may relation to atrial fibrillation. The effect of KCNFA E145D variation on the function of IKa channel is to be determined.

关 键 词：心房颤动 钾通道 多态性 单核苷酸 基因 

分 类 号：R541.75[医药卫生—心血管疾病]