高通量测序多基因检测对家族性心房颤动的预测价值  

Forecasting familial atrial fibrillation by high-throughput sequencing for polygenic detection

作　　者：刘俊[1] 陈舒 应璇 叶晓霞[1] 董扬[1] 王文标[1] LIU Jun;CHEN Shu;YING Xuan;YE Xiao-xia;DONG Yang;WANG Wen-biao(Department of Cardiovascular Medicine of Jinhua People′s Hospital,Jinhua 321000,Zhejiang,China)

机构地区：[1]金华市人民医院心血管内科,浙江金华321000

出　　处：《中国心脏起搏与心电生理杂志》2020年第4期345-349,共5页Chinese Journal of Cardiac Pacing and Electrophysiology

基　　金：金华市科技计划项目(项目编号:2017-4-011)。

摘　　要：目的探讨KCNQ1、KCNE2、SCN5A等致病基因在家族性、非家族性心房颤动(简称房颤)患者及正常无房颤者中的检出率,并分析致病基因与家族性房颤(FAF)的相关性及其预测价值。方法应用随机数字表法选取2017年1月至2018年10月间于金华市人民医院就诊的40例FAF患者作为FAF组,并选取20例同期非FAF患者纳入非FAF组,以及20例正常无房颤者作对照组。收集所有患者临床资料,并采集患者外周血进行高通量测序检测致病基因KCNQ1、KCNE2、SCN5A、KCND3、CJA5、ACC9突变情况,经计算机分析系统进行碱基读取、DNA序列获得。比较三组患者致病基因突变检出率,并分析上述致病基因与FAF相关性及其对FAF的预测价值。结果单因素分析显示,三组致病基因KCNQ1、KCNE2、SCN5A突变检出率存在统计学意义(P<0.05)。多因素Logistic回归分析显示,致病基因KCNQ1(OR=36.013,P=0.003)、SCN5A(OR=42.175,P=0.002),KCNE2(OR=6.977,P=0.033)突变均为FAF的独立危险因素。KCNQ1(+)、KCNE2(+)、SCN5A(+)诊断FAF的灵敏度分别为70.0%、60.0%、62.5%,特异度分别为80.0%、85.0%、82.5%。不同致病基因单独检测的诊断效能比较均无明显差异(P>0.05)。致病基因KCNQ1(+)、KCNE2(+)、SCN5A两两联合检测(灵敏度85.0%、85.0%、82.5%,特异度75.0%、67.5%、77.5%)与三者联合检测(灵敏度95.0%,特异度67.5%)的诊断效能无明显差异(P>0.05)。结论应用高通量测序多基因检测技术可有效检测FAF患者致病基因突变情况,基因KCNQ1、KCNE2、SCN5A突变与FAF密切相关,这些基因变异情况的联合检测对FAF具有一定预测价值。Objective To explore detection rate of pathogenicity genes such as KCNQ1、KCNE2、SCN5 A in familial atrial fibrillation(FAF)patients,non-FAF patients and normal person without atrial fibrillation,analysing the correlation between pathogenicity genes and FAF,and their predictive value on FAF. Methods Forty FAF patients treated in Jinhua people′s hospital were employed as FAF group by random number table method from January 2017 to October 2018,20 non-FAF patients were employed as non-FAF group,and 20 normal person without atrial fibrillation were employed as control group.All patients′clinical data were collected,collecting patients′peripheral blood to perform high-throughput sequencing for detect gene mutation of KCNQ1、KCNE2、SCN5 A、KCND3、CJA5、ACC9,base sequence reading and DNA sequence obtaining performed by computer.Detection gene mutation rate of pathogenicity genes of three groups were comparatively analyzed,and analysing pathogenicity genes′predictive value on FAF and the correlation between pathogenicity genes and FAF. Result Simple correlation showed that there was a statistical difference among three groups in detection gene mutation rate of KCNQ1、KCNE2、SCN5 A(P<0.05). Multivariate Logistic regression analysis showed that gene mutation of KCNQ1(OR=36.013,P=0.003)、SCN5 A(OR=42.175,P=0.002),KCNE2(OR=6.977,P=0.033)were risk factors of FAF.The sensitivity of KCNQ1(+),KCNE2(+),SCN5 A(+)to diagnose FAF was 70.0%,60.0%,62.5% respectively,the specificity was 80.0%,85.0%,82.5% respectively.There was no significant different among different pathogenicity genes single detection in diagnostic efficiency(P>0.05).There was no significant different among pairwise combination of KCNQ1(+),KCNE2(+)and SCN5 A(+)(the sensitivity was85.0%,85.0%,82.5%;the specificity was 75.0%,67.5%,77.5%)and all three combined diagnosis(sensitivity 95.0%,specificity 67.5%)in diagnostic efficiency(P>0.05). Conclusion Using high-throughput sequencing for polygenic detection can effectively detect pathogenicity genes gen

关 键 词：心血管疾病 高通量测序 家族性心房颤动 致病基因 预测价值 

分 类 号：R541.75[医药卫生—心血管疾病]