ARVD/C患者PKP2、TGFβ3基因突变与心功能及预后的关系  

Relationship between PKP2 and TGFβ3 Gene Mutations and Cardiac Function and Prognosis in Patients with ARVD/C

作　　者：张曼 苗睿 高淑贤 郭晓宁 郝亚逢[1] 王献忠[1] ZHANG Man;MIAO Rui;GAO Shuxian;GUO Xiaoning;HAO Yafeng;WANG Xianzhong(The Second Department of Cardiology,Handan First Hospital,Handan 050000,Hebei,China)

机构地区：[1]邯郸市第一医院心内二科,河北邯郸050000

出　　处：《中国分子心脏病学杂志》2023年第3期5422-5426,共5页Molecular Cardiology of China

基　　金：河北省卫生健康委员资助项(20220498)。

摘　　要：目的分析致心律失常性右室心肌病(arrhythmogenic right ventricular cardiomyopathy,ARVD/C)患者血小板亲核蛋白2(plakophilin-2,PKP2)、转化生长因子β3(transforming growth factorβ3,TGFβ3)基因突变与患者心功能以及预后的关系。方法收集2017年1月至2021年1月收治的82例ARVD/C患者的临床资料,检查患者超声心动图,记录右心室半径、Epsilon波情况、左心室是否受累等指标,留取患者外周血。选取同期90例健康者为对照组,提取研究对象基因组DNA,PCR法扩增PKP2、TGFβ3基因的DNA片段,测序法测定研究对象PKP2、TGFβ3基因突变情况。比较对照组与ARVD/C患者、不同心功能分级(心功能Ⅱ级、Ⅲ级、Ⅳ级)ARVD/C患者、不同预后情况(预后良好、预后不良)等组间PKP2、TGFβ3基因突变的差异,分析PKP2、TGFβ3基因突变与临床病理参数以及预后的关系。结果与对照组相比,ARVD/C组患者PKP2、TGFβ3基因突变率升高(P<0.05)。ARVD/C患者共检测出7个PKP2位点突变(5例包含多个PKP2位点突变),2个TGFβ3位点突变(7例包含这2个位点突变)。与心功能Ⅱ级ARVD/C患者相比,心功能Ⅲ级、Ⅳ级ARVD/C患者PKP2、TGFβ3基因突变率升高(P<0.05);与心功能Ⅲ级ARVD/C患者相比,心功能Ⅳ级ARVD/C患者PKP2、TGFβ3基因突变率升高(P<0.05)。PKP2突变患者晕厥比例、累及左心室比例、有Epsilon波比例高于PKP2未突变者(P<0.05);TGFβ3突变患者晕厥比例、累及左心室比例、有Epsilon波比例高于TGFβ3未突变患者(P<0.05)。与预后良好组相比,预后不良组ARVD/C患者PKP2、TGFβ3基因突变率升高(P<0.05)。结论PKP2、TGFβ3突变与ARVD/C患者的发病、心功能以及预后情况相关,为ARVD/C患者的分层治疗提供了参考依据。Objective To analyze the relationship between plakophilin-2(PKP2)and transforming growth factorβ3(TGFβ3)gene mutations and cardiac function and prognosis in patients with arrhythmogenic right ventricular cardiomyopathy(ARVD/C).Methods The clinical data of 82 patients with ARVD/C between January 2017 and January 2021 were collected,the echocardiograms was examined,and the right ventricular radius,Epsilon wave,and whether the left ventricle was involved were recorded,the peripheral blood of the patients was collected,90 healthy subjects were selected as the control group during the same period.The genomic DNA of the research subjects was extracted,the DNA fragments of the PKP2 and TGFβ3 genes were amplified by PCR,and the PKP2 and TGFβ3 gene mutations of the research subjects were determined by sequencing,the differences in PKP2 and TGFβ3 gene mutations between control group and ARVD/C patients,among ARVD/C patients with functional (gradeⅢ,cardiac function gradeⅣ)and different prognosis(good prognosis,poor prognosis)were analyzed,and the relationship between PKP2 and TGFβ3 gene mutations and clinicopathological parameters and prognosis was analyzed.Results Compared with the control group,the mutation rates of PKP2 and TGFβ3 genes in the ARVD/C group was increased(P<0.05).A total of 7 PKP2 site mutations were detected in ARVD/C patients,5 patients contained multiple site mutations;and 2 site mutations were detected in TGFβ3,and 7 patients contained two site mutations.Compared with patients with classⅡARVD/C,the mutation rates of PKP2 and TGFβ3 genes in patients with classⅢandⅣARVD/C were higher(P<0.05);compared with ARVD/C patients with gradeⅢcardiac function,the mutation rates of PKP2 and TGFβ3 genes in ARVD/C patients with gradeⅣcardiac function were higher(P<0.05).The proportion of syncope,involvement of left ventricle,and Epsilon wave in patients with PKP2 mutation were higher than those in patients without PKP2 mutation(P<0.05);the proportion of syncope,involvement of left ventricle,and

关 键 词：致心律失常性右室心肌病 血小板亲核蛋白2 转化生长因子Β3 

分 类 号：R542.2[医药卫生—心血管疾病] R541.7[医药卫生—内科学]