中国孤立性心房颤动肺静脉肌袖发育基因垂体同型框2的突变筛查及相应临床特征  

Mutation screen of pulmonary myocardium development gene pituitary homeobox 2 in Chinese patients with isolated atrial fibrillation

作　　者：马继芳[1] 张睿[1] 李硕[1] 孙健[1] 王群山[1] 董洁[2] 郑谷燕[2] 丰明俊[3] 陈晓敏[3] 李毅刚[1] 

机构地区：[1]上海交通大学医学院附属新华医院心内科,上海200092 [2]北京大学分子医学研究所人类群体遗传学研究室 [3]宁波大学医学院附属第一医院心内科

出　　处：《上海医学》2011年第8期616-619,565,共4页Shanghai Medical Journal

基　　金：国家自然科学基金(30871082);2010年度上海市优秀学科带头人计划(10XD1402800)资助项目

摘　　要：目的对孤立性心房颤动(AF)患者进行垂体同型框2(PITX2)基因的突变扫描,并分析突变患者的相应临床特点。方法对160例孤立性AF患者和200名健康者的PITX2基因进行突变扫描。采用聚合酶链反应(PCR)扩增PITX2基因,通过单链构象多态性技术筛查突变,对发现异常的个体采用双脱氧核苷链末端合成终止法进行直接测序。采用Sequence scanner v 1.0软件分析测序图。结果在2例永久性AF患者中发现位于内含子区域的新改变g.766C>A、位于5’UTR区域的新改变g.8310C>T(c.-150C>T)。这两例携带者对药物及电复律治疗的反应较差,接受环肺静脉消融手术后,随访1年未再复发。200名健康者中未发现此改变。结论首次在中国孤立性AF患者中发现影响肺静脉肌袖发育基因PITX2的非编码区改变,其可能为我们进一步理解肺静脉肌袖在AF的发病过程中的作用提供新的启示。Objective To screen for the mutations of pituitary homeobox 2（PITX2） gene in Chinese patients with isolated atrial fibrillation and analyze the corresponding clinical characteristics of PITX2 variations.Methods A total of 16 patients with isolated atrial fibrillation and 200 age-matched healthy control subjects were enrolled in the present study.Exons of PITX2 gene were firstly amplified by RT-PCR,and the PCR products were screened by single strand conformation polymorphism analysis;the abnormal patients were subjected to direct sequencing using the dideoxynucleotide chain termination DNA sequencing method.The sequencing results were analyzed by Sequence scanner v1.0.Results We identified a novel intronic variant g.766CA and a novel substitution g.8310CT（c.-150CT） in the 5＇UTR areas of PITX2 gene in two permanent atrial fibrillation patients,who were resisted to drug and electrical conversion therapy;they received circumferential pulmonary vein ablation surgery and free of recurrence after one year follow-up.The above 2 novel variants were not seen in the 200 control subjects.Conclusions We have for the first time indentified non-coding variations in PITX2 in Chinese patients with isolated atrial fibrillation,which may provide a new insight for the mechanisms of isolated atrial fibrillation.

关 键 词：心房颤动 基因 突变 垂体同型框2 转录因子 

分 类 号：R541.75[医药卫生—心血管疾病]