Novel GATA5 loss-of-function mutations underlie familial atrial fibrillation.
Novel GATA5 loss-of-function mutations underlie familial atrial fibrillation.
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新型 GATA5 功能丧失突变是家族性心房颤动的基础
DOI：
10.6061/clinics/2012(12)08
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发表时间：
2012-12
期刊：
影响因子：
--
通讯作者：
Yang YQ
中科院分区：
文献类型：
--
作者：
Gu JY;Xu JH;Yu H;Yang YQ
目的：本研究旨在鉴定家族性房颤背后的新型GATA5突变。方法：共招募110例不相关的家族性心房颤动患者和200例不相关的、种族匹配的健康对照。在110个房颤先证者中对GATA5基因的整个编码区进行了测序。随后对突变携带者的亲属和200名对照进行基因分型。利用荧光素酶报告基因检测系统对突变的GATA5的功能效应进行了表征。结果：在110个不相关心房颤动家族中的两个家族中发现了两个新的杂合GATA5突变（p.Y138F和p.C210G）。这些错义突变在家族中与AF共分离，在400条对照染色体中不存在。对GATA5蛋白序列的跨物种比对表明，改变的氨基酸在进化上是完全保守的。功能分析显示，与野生型相比，突变体GATA5蛋白的转录激活显著降低。结论：这一发现扩大了与房颤相关的GATA5突变的范围，并为房颤发病的分子机制提供了新的见解，为这种常见心律失常的早期预防和个性化治疗提供了潜在的意义。
OBJECTIVE: This study aimed to identify novel GATA5 mutations that underlie familial atrial fibrillation. METHODS: A total of 110 unrelated patients with familial atrial fibrillation and 200 unrelated, ethnically matched healthy controls were recruited. The entire coding region of the GATA5 gene was sequenced in 110 atrial fibrillation probands. The available relatives of the mutation carriers and 200 controls were subsequently genotyped for the identified mutations. The functional effect of the mutated GATA5 was characterized using a luciferase reporter assay system. RESULTS: Two novel heterozygous GATA5 mutations (p.Y138F and p.C210G) were identified in two of the 110 unrelated atrial fibrillation families. These missense mutations cosegregated with AF in the families and were absent in the 400 control chromosomes. A cross-species alignment of GATA5 protein sequence showed that the altered amino acids were completely conserved evolutionarily. A functional analysis revealed that the mutant GATA5 proteins were associated with significantly decreased transcriptional activation when compared with their wild-type counterpart. CONCLUSION: The findings expand the spectrum of GATA5 mutations linked to AF and provide novel insights into the molecular mechanism involved in the pathogenesis of atrial fibrillation, suggesting potential implications for the early prophylaxis and personalized treatment of this common arrhythmia.
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华法林剂量用于慢性心房颤动老年患者的抗凝治疗。
DOI：
10.6061/clinics/2012(06)01
发表时间：
2012
期刊：
Clinics (Sao Paulo, Brazil)
影响因子：
--
作者：
Mansur Ade P;Takada JY;Avakian SD;Strunz CM
通讯作者：
Strunz CM
影响因子：
6.1
作者：
Bittner, Alex;Moennig, Gerold;Eckardt, Lars
通讯作者：
Eckardt, Lars
影响因子：
--
作者：
FEINBERG, WM;SEEGER, JF;PEARCE, LA
通讯作者：
PEARCE, LA
影响因子：
8.3
作者：
WOLF, PA;ABBOTT, RD;KANNEL, WB
通讯作者：
KANNEL, WB
影响因子：
9.9
作者：
WOLF, PA;DAWBER, TR;KANNEL, WB
通讯作者：
KANNEL, WB