GATA4基因与单纯性先天性心脏病的相关性研究

Association analysis of GATA4 gene and congenital heart disease

目的探讨GATA4基因与单纯性先天性心脏病的相关性。方法2001年,收集沈阳军区总医院心脏外科62个单纯性先天性心脏病(CHD)家系,选择GATA4基因编码区内4个可引起氨基酸改变的cSNP,应用聚合酶链反应-限制性片段长度多态性技术(PCR-RFLP)分析该62个单纯性CHD核心家系206名成员的基因型;应用ETDT软件进行单位点关联分析;应用2LD软件进行配对连锁不平衡检验;应用TRANSMIT软件进行单体型分析。结果Q19E(rs1139240)位点未检测到多态。L39V(rs1139241)、P66A(rs1139244)和G377S(rs3729856)位点存在多态。单位点关联分析显示L39V位点χ2=6·178(P<0·05),P66A位点χ2=8·607(P<0·05),G377S位点χ2=9·842(P<0·05)。配对连锁不平衡检验显示L39V和P66A之间存在连锁不平衡(D’=0·999999)。单体型分析共观察到4种单体型,只有2种单体型的频率大于3%,但却占单体型总数的97·7%。这两种单体型的总体统计χ2=1·0345(P>0·05)。结论Q19E在本文人群中未检测到多态;L39V、P66A和G377S3个位点与单纯性CHD有明显的相关性(P<0·05)。

Objective To discuss the association between GATA4 gene and congenital heart disease. Methods Four cSNPs were selected that could result in changing of amino acids in the coding re,on of GATA4 gene, and performed PCR-RFLP in 206 members from 62 congenital heart disease nuclear pedigree. The association of individual SNP was analyzed using ETDT software. Linkage disequilibrium was analyzed with 2LD. Haplotype was built using TRANSMIT software. Results Polymorphism was not detected at Q19E （ rs1139240 ） among the four cSNP. The association analysis of individual SNP showed significant association at L39V （ χ^2 = 6. 178, P 〈 0. 05 ）, P66A （ χ^2 = 8. 607, P 〈 0. 05 ） and G377S （χ^2 =9. 842, P 〈0. 05）. There existed linkage disequilibrium （D＇ =0. 999999） between L39V and P66A. Four haplotypes were observed in haplotype analysis, but the globe P value was not significant （ χ^2 = 1. 0345 ）. Conclusion Polymorphism is not detected at Q19E among the northeastern people of China. There is significant association of L39V, P66A and G377S with simple CHD.