Analysis Of The GATA-4 Gene In Three Atrial Septal Defect Family

[Objective]Congenital Heart Disease(CHD) is an inborn abnormality which seriously threatens infants' health.The morbidity is from 0.3%to 1%in survival births,and even up to 10.2%in abortus Atrial Septal Defect(ASD) is one of the most common type that belongs to CHD.As a complex disease,CHD mainly appeared in embryonic heart in vulnerable period during the development.ASD and other CHD result from the interaction of genetic factors and environmental agent.Abnormality of heart-associated gene and their production lead to abnormality embryonic development.The details of genetic factors and the mechanism have not been known at present.The genetic factors may play a decisive role in the occurring of Familial Atrial Deptal Defect(FASD),which is a good sample in the studying of ASD.GATA-4(GATA binding factor-4),as one of the transcription factors,is closely related to the process of heart development.GATA-4 gene was deteced to locate at human chromosome 8 in 1995,and more exactly at 8p23.1→p22 by fluorescence in situ hybridization in 1996.Abroad researches discovered some kinds of meaningful mutations in GATA-4 gene in simple CHD pedigrees.There are no reports about the relationship among cSNP,STR and FASD in GATA-4 gene at present.We selected 4 cSNPs(Coding-region single nucleotide polymorphisms) and 16 STR sites which could cause amino acids changes in coding region of GATA-4 gene from ASD families,then analyzed the mutation of cSNPs and STR in 3 core pedigrees of FASD, in the hope to find the potential mechanism of GATA-4 gene in causing the ASD.[Methods]Three Atrial Septal Defect(ASD) families including 6 patients were collected as experimental group.15 healthy individuals without the evidences of ASD were collected as control group.Samples were collected during the cardiac surgery,in Cardiovascular Disease Hospital,Yunnan Province.4 cSNP(which may change the amino acids) in the coding region of GATA-4 gene,11 STR sites near the GATA-4 gene and 5 STR sites in GATA-4 gene were given PCR and DNA analysis. [Results]Polymorphism was discovered in D8S258 in family 2.Polymorphism was discovered in D8S552 in both family 1 and family 2.Neither mutation nor polymorphism was showed in cSNP Q19E(rs1139240),L39V(rs1139241),P66A (rs1139244) and G377S(rs3729856) sites in three families.[Conclusion]Polymorphism of D8S258,D8S552 were found in the subjects in our research.Mutations of D8S258,D8S552 were not found in the subjects in our research.No mutation was detected in 4 cSNP sites.The mutation of coding region of GATA-4 gene was not found in these subiects.