GATA6基因与先天性心脏病发病的关系

The relationship between gene GATA6 defect and congenital heart disease

近期研究发现GATA6可能是先天性心脏病的一个致病候选基因，其编码产物GATA6转录因子是GATA转录因子家族中的一员，在心脏发育早期表达于胚胎中胚层，可以单独或与其他转录因子协同作用于心脏发育。近年对心脏流出道发育机制的研究发现，GATA6可以调控心脏神经嵴细胞向心脏流出道迁移。通过测序技术对GATA6外显子测序，找到多个非同义氨基酸突变（P．A178V、P．L198V、P．D404Y、P．E460X）。这些突变会影响GATA6转录因子转录功能，并与先天性心脏病发病密切相关。在体内适当表达水平的GATA6对正常心脏发育是必须的，过表达的GATA6会引起胚胎心脏发育异常。GATA6转录因子可以与其他对心脏特异性转录因子相互作用，精密调控整个心脏发育过程。该文阐述GATA6基因与先天性心脏病发生关系的研究进展。

Recent studies have showed GATA6 may be a candidate gene of congenital heart disease （CHD）. GATA6 is a member of the GATA transcription factors, and GATA6 is expressed within the precardiac mesoderm from early stages in its specification. Some studies about outflow tract （OFT） development show that GATA6 can directly regulate the migration of cardiac neural crest cells. Researchers find some missense mutation on GATA6 （ p. A 178 V, p. L198 V, p. D404Y, p. E460X） by directly sequencing. These mutations may influence transcriptional activity of GATA6 and are closely associated with CHD. Appropriate level of GATA6 in embryos is critical to cardiogenesis, and over-expression GATA6 can disrupt this process. Cardiogenesis needs a cascade of transcription factors includes GATA6 and other factors under tight temporal and spatial control. This paper reviews the latest studies about the relationship between gene GATA6 defect and CHD.