NKX2-6 mutation predisposes to familial atrial fibrillation.
NKX2-6 mutation predisposes to familial atrial fibrillation.
复制标题
NKX2-6 突变易患家族性房颤。
DOI：
10.3892/ijmm.2014.1971
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发表时间：
2014-12
影响因子：
5.4
通讯作者：
Yang Yi-Qing
中科院分区：
文献类型：
--
作者：
Wang Jun;Zhang Dai-Fu;Sun Yu-Min;Li Ruo-Gu;Qiu Xing-Biao;Qu Xin-Kai;Liu Xu;Fang Wei-Yi;Yang Yi-Qing
心房颤动（AF）是持续性心律失常的最常见形式，并与发病率和死亡率显著增加相关。越来越多的证据表明，遗传缺陷参与了AF的发病机制，并已确定了许多AF相关基因。然而，AF是一种遗传异质性疾病，绝大多数患者中支持AF的遗传成分仍不清楚。在这项研究中，对150例无血缘关系的孤立性房颤患者的NK 2同源框6（NKX 2 -6）基因（编码对心血管发育重要的同源域转录因子）的整个编码外显子和剪接点进行测序，并在索引患者中鉴定出一种新的杂合NKX 2 -6突变p.Q175H。对突变携带者现有家庭成员的遗传分析显示，该突变与AF以常染色体显性模式传播共分离。错义突变是不存在的200无关的种族匹配的健康个体作为对照，改变的氨基酸是完全保守的物种之间的进化。由于NKX 2 -6的转录靶点未知，因此使用NKX 2 -5作为替代物分析了突变在转录活性方面的功能特征。人NKX 2 -6和NKX 2 -5蛋白质之间的比对显示，Q175 H突变的NKX 2 -6与Q181 H突变的NKX 2 -5等同，并且将Q181 H引入NKX 2 -5显著降低了其在心房利钠因子启动子处的转录活性。本研究首次将NKX 2 -6基因缺陷与房颤易感性增强联系起来，为房颤的产前预防和个性化治疗提供了新的思路。
Atrial fibrillation (AF) is the most common form of sustained cardiac arrhythmia and is associated with substantially increased morbidity and mortality rates. Aggregating evidence demonstrates that genetic defects are involved in the pathogenesis of AF and a number of AF-associated genes have been identified. Nevertheless, AF is a genetically heterogeneous disorder and the genetic components underpinning AF in an overwhelming majority of patients remain unclear. In this study, the entire coding exons and splice junction sites of the NK2 homeobox 6 (NKX2-6) gene, which encodes a homeodomain transcription factor important for cardiovascular development, were sequenced in 150 unrelated patients with lone AF, and a novel heterozygous NKX2-6 mutation, p.Q175H, was identified in an index patient. Genetic analysis of the available family members of the mutation carrier revealed that the mutation co-segregated with AF transmitted in an autosomal dominant pattern. The missense mutation was absent in the 200 unrelated ethnically matched healthy individuals used as controls and the altered amino acid was completely conserved evolutionarily among species. Due to unknown transcriptional targets of NKX2-6, the functional characteristics of the mutation as regards transcriptional activity were analyzed using NKX2-5 as a surrogate. Alignment between human NKX2-6 and NKX2-5 proteins displayed that the Q175H-mutant NKX2-6 was equivalent to the Q181H-mutant NKX2-5, and the introduction of Q181H into NKX2-5 significantly decreased its transcriptional activity at the atrial natriuretic factor promoter. The present study firstly associates genetically defective NKX2-6 with enhanced susceptibility to AF, providing novel insight into the molecular mechanisms underlying AF and suggesting potential strategies for the antenatal prophylaxis and personalized treatment of AF.
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影响因子：
39
作者：
Soliman, Elsayed Z.;Safford, Monika M.;Muntner, Paul;Khodneva, Yulia;Dawood, Farah Z.;Zakai, Neil A.;Thacker, Evan L.;Judd, Suzanne;Howard, Virginia J.;Howard, George;Herrington, David M.;Cushman, Mary
通讯作者：
Cushman, Mary
DOI：
10.1161/circep.108.779181
发表时间：
2009-06
期刊：
Circulation. Arrhythmia and electrophysiology
影响因子：
--
作者：
Watanabe H;Darbar D;Kaiser DW;Jiramongkolchai K;Chopra S;Donahue BS;Kannankeril PJ;Roden DM
通讯作者：
Roden DM
影响因子：
5.5
作者：
Abed, Hany S.;Samuel, Chrishan S.;Sanders, Prashanthan
通讯作者：
Sanders, Prashanthan
影响因子：
37.8
作者：
Go AS;Mozaffarian D;Roger VL;Benjamin EJ;Berry JD;Blaha MJ;Dai S;Ford ES;Fox CS;Franco S;Fullerton HJ;Gillespie C;Hailpern SM;Heit JA;Howard VJ;Huffman MD;Judd SE;Kissela BM;Kittner SJ;Lackland DT;Lichtman JH;Lisabeth LD;Mackey RH;Magid DJ;Marcus GM;Marelli A;Matchar DB;McGuire DK;Mohler ER 3rd;Moy CS;Mussolino ME;Neumar RW;Nichol G;Pandey DK;Paynter NP;Reeves MJ;Sorlie PD;Stein J;Towfighi A;Turan TN;Virani SS;Wong ND;Woo D;Turner MB;American Heart Association Statistics Committee and Stroke Statistics Subcommittee
通讯作者：
American Heart Association Statistics Committee and Stroke Statistics Subcommittee
DOI：
10.1016/j.bbrc.2010.06.042
发表时间：
2010-07-16
影响因子：
3.1
作者：
Wang, Pengyun;Yang, Qinbo;Wu, Xiaofen;Yang, Yanzong;Shi, Lisong;Wang, Chuchu;Wu, Gang;Xia, Yunlong;Yang, Bo;Zhang, Rongfeng;Xu, Chengqi;Cheng, Xiang;Li, Sisi;Zhao, Yuanyuan;Fu, Fenfen;Liao, Yuhua;Fang, Fang;Chen, Qiuyun;Tu, Xin;Wang, Qing K.
通讯作者：
Wang, Qing K.