特发性房颤相关GATA5基因新突变的识别  

Identification of novel GATA5 mutations associated with idiopathic atrial fibrillation

作　　者：于泓[1] 刘晓利[1] 马文林[1] 丁可可[1] 陈惠卿[1] 戴洁[1] 

机构地区：[1]同济大学附属同济医院心内科,上海200065

出　　处：《国际心血管病杂志》2012年第6期377-380,384,共5页International Journal of Cardiovascular Disease

基　　金：上海市浦江人才计划项目(PJ30425016)

摘　　要：目的:识别特发性房颤(AF)相关GATA5基因新突变。方法:收集120例无血缘关系的特发性AF患者和200名无血缘关系且种族匹配的健康对照者的临床资料和血标本。抽提基因组DNA,通过聚合酶链反应扩增AF候选基因GATA5的全部外显子及其两侧的部分内含子,采用双脱氧核苷链末端合成终止法对全部扩增片段进行测序。将所测的序列与GenBank数据库中的GATA5基因序列进行比对,以发现GATA5基因突变。应用多序列比对软件ClustalW评估突变氨基酸的保守性,应用致病性预测软件MutationTaster预测突变的致病性。结果:在2例AF患者各发现1个新的GATA5基因杂合错义突变,突变率约为1.67%。突变分别为GATA5基因编码核苷酸序列第668位的腺嘌呤(adenine,A)变为胸腺嘧啶(thymine,T),即c.668A>T突变;第863位的A变为胞嘧啶(cytosine,C),即c.863A>C突变。多序列比对显示2种突变氨基酸在进化上均高度保守,致病性预测表明2种突变均有致病性。结论:本研究识别出AF相关GATA5基因新突变,有助于揭示AF发生的分子机制。Objective： To identify novel GATA5 mutations associated with idiopathic atrial fibrillation （AF）. Methods：The clinical data and blood samples from a cohort of 120 unrelated patients with AF and a total of 200 unrelated, ethnically matched healthy individuals as controls were collected. The genornic DNA from all the subjects was extracted using the corresponding kits. The whole exons and flanking partial introns of the candidate gene, GATA5, were amplified by polymerase chain reaction, and the amplicons were sequenced with the di-deoxynucleotide chain termination technique. The sequence variations were identified by alignment of the acquired sequences with those of GATA5 released in GenBank. The software ClustalW for alignment of multiple sequences was used to evaluate whether an altered amino acid is evolutionarily conservative. The software MutationTaster was used to predict the pathogenic probability of a mutation. Results：Two novel heterozygous missense mutations of GATA5 were identified in 2 AF patients, respectively, with a prevalence of approximately 1.67% One is the substitution of thymine （T） for adenine （A） at nucleotide 668 of the coding sequence of GATA5 （c. 668A〉T）, and the other is the transition of A into cytosine （C） at coding nucleotide 863 （c. 863A〉C）. Alignment of multiple GATA5 proteins across species showed that the altered amino acids were highly conservative. The 2 identified mutations were both predicted to be disease-causing. Conclusion： Novel GATA5 mutations linked to AF are identified in this study, which contributes to reveal the molecular mechanism involved in AF.

关 键 词：心律失常 特发性房颤 遗传学 转录因子 GATA5 

分 类 号：R541.7[医药卫生—心血管疾病]