SHOX2基因与特发性心房颤动的关系研究

The relationship between SHOX2 gene and idiopathic atrial fibrillation

目的:研究SHOX2基因与特发性心房颤动(IAF)的关系。方法:收集178例汉族IAF患者和218名匹配的健康对照者。通过聚合酶链反应-DNA测序分析SHOX2基因的编码外显子及剪接序列。将测出的序列与核苷酸数据库中的SHOX2序列进行对比,查找SHOX2基因突变。通过在线计算机程序MUSCLE评估突变氨基酸进化上的保守性,应用PolyPhen-2、MutationTaster和PROVEAN软件分析SHOX2基因突变的致病性。结果:在1例IAF患者中发现SHOX2基因新突变,c.632G>C(p.Trp211Ser),该错义突变不存在于218名健康对照者中,多物种SHOX2蛋白序列比对分析显示被改变氨基酸在进化上完全保守,致病性预测表明所识别的SHOX2基因突变具有致病性。结论:c.632G>C是基因新突变,对IAF的早期防治具有潜在的临床意义。

Objective:To investigate the relationship between the SHOX2 gene and idiopathic atrial fibrillation (IAF). Methods:One hundred and seventy-eight unrelated patients of Han nationality with IAF and 218 matched healthy volunteers were enrolled.Comparison analysis of the obtained sequences and SHOX2 sequences from the Nucleotide database was done to identify a novel SHOX2 mutation.The online computer program of MUSCL was utilized to evaluate whether the mutated amino acid was evolutionarily conserved.The disease-causing potential of the identified SHOX2 mutation was evaluated with PolyPhen-2,MutationTaster and PROVEAN. Results:A new heterozygous SHOX2 mutation c.632G >C,equivalent to p.Trp211Ser,was detected in a sporadic IAF patient.The missense mutation was absent in the 218 control individuals.The altered amino acid was completely conserved evolutionarily,and the mutation was predicted to be causative. Conclusions:c.632G>C is a new SHOX2 mutation with potential clinical implications for the prophylaxis and treatment of IAF.