Transcription Factors Nkx2.5 And Gata4 Gene Polymorphism With Six Congenital Heart Disease, Ventricular Septal Defect Pedigree

The correlational exploration on the relationship of NKX2.5 gene and GATA4 gene as well as six congenital heart diseases:ventricular septal defect family[Objective] Congenital heart disease(CHD) is the most common disease of all birth defects, which is an important cause of severe death and disability in infant. The morbidity of ventricular septal defect (VSD) in CHD in newborn is 20%, in children is 30%, which is the highest rates of all CHD. If the gene which controls the development of heart has mutate that can cause CHD. Therefore, to seek gene relevant to VSD becomes one focus in the field of genetics study. In the large number of genes in present research, NKX2.5 and GATA4 are closely related to participate in normal developmental processes of heart, which have different time and space expression.They can adjust the normal development of heart, any influence on their normal expression which may cause the heart malformation. In the view of family, this research is to investigate the relationship of gene polymorphisms in NKX2.5 and GATA4 gene and CHD, aim at finding the potential mechanism of NKX2.5 and GATA4 gene in causing the CHD, offering effective evidence on experiments.[Methods] Six Ventricular Septal Defect (VSD) families including 10 patients were collected as experimental group,20 healthy individuals without the evidences of VSD were collected as control group. And in accordance with clinical data established family genealogy and extracted DNA from blood samples. Using PCR amplification and DNA direct sequencing analysis of NKX2.5 and GATA4 gene exons and the 3'UTR part of the region to detect gene polymorphisms. And we analyzed all polymorphic loci associated with ventricular septal defect (VSD).[Results]1. Initially established DNA database and clinical information of part of the ventricular septal defect family pedigree in Yunnan province;2. Mutation on rs2277923 polymorphism in VSD patients and normal subjects were detected in the NKX2.5 gene exon 1;3. One C＞A synonymous mutant locus was discovered in NKX2.5 gene 3' untranslated region only in father and son in familyⅢ, but was not discovered in other family pedigree members;4. Mutant locus was not found in single nucleotide polymorphisms detected by GATA4 gene exon 6.[Conclusion]1. We have collected six clinical data of VSD family pedigree to enrich the VSD genetic resource information;2. Polymorphism was discovered in rs2277923 in NKX2.5 gene exon 1, but we think the relationship between this synonymous mutations point and CHD incidence still needs further study;3. For the first time in China on the NKX2.5 gene locus polymorphism rs703752 coverage, and the results suggest that the mutation relate to the pathogenesis of CHD;4. The result of the research for further research in this field has important reference value for the subsequent research also has instructive value for genetic screening and genetic diagnosis.