GLI1基因I495L和D933G多态性与先天性心脏病的相关性

Association between I495L and D933G Polymorphisms of Glioma-Associated Oncogene Homolog 1 Gene and Congenital Heart Disease

目的探讨GLI1基因I495L和D933G多态性与先天性心脏病(CHD)的相关性。方法采用病例对照研究,选择180例CHD患儿[病例组,包括ASD37例、VSD65例及法洛四联症(TOF)78例]和200名健康体检儿童(健康对照组)。应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)进行GLI1基因I495L和D933G位点多态性检测,分析上述2个多态位点基因型频率和等位基因频率在病例组和对照组的分布,比较各个位点不同基因型与CHD患病风险的关系。应用SPSS13.0软件进行统计学分析。结果 GLI1基因I495L多态位点基因型频率在VSD组、TOF组的分布与健康对照组比较差异有统计学意义(P=0.024,0.029),等位基因频率的分布亦存在统计学差异(P=0.015,0.004),且C等位基因携带者患VSD和TOF的风险高于A等位基因携带者(VSD:OR=1.658,95%CI1.101～2.496;TOF:OR=1.757,95%CI1.198～2.575);GLI1基因D933G多态位点基因型频率在VSD组、TOF组的分布与健康对照组比较存在统计学差异(P=0.015,0.018),等位基因频率的分布亦存在统计学差异(P=0.039,0.008),且G等位基因携带者患VSD和TOF的风险高于A等位基因携带者(VSD:OR=1.520,95%CI1.020～2.266;TOF:OR=1.654,95%CI1.137～2.406)。结论 GLI1基因I495L和D933G多态性与CHD具有明显的相关性,具有C、G等位基因的个体患CHD的风险增高。

Objective To investigate the association between the I495L,D933G polymorphisms of glioma-associated oncogene homolog 1（GLI1）gene and congenital heart disease（CHD）.Methods Under the case-control study,the I495L and D933G polymorphisms of GLI1 gene in 180 children with CHD,including 37 children with atrial septal defect（ASD）,65 children with ventricular septal defect（VSD）and 78 children with tetralogy of Fallot（TOF）,and 200 healthy children,were detected with polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP）.The distribution of genotype and allele frequency at above 2 polymorphism sites and its relationship with the risk of CHD were analyzed in these groups.SPSS 13.0 software was used to analyze the data.Results The distribution of genotype and allele frequency at I495L polymorphism site were significantly different between VSD group,TOF group and healthy control group（P=0.024,0.029;P=0.015,0.004）,and the relative risks for VSD and TOF in C allele carriers were higher than those in A allele carriers（VSD：OR=1.658,95%CI 1.101-2.496;TOF：OR=1.757,95%CI 1.198-2.575）.The distribution of genotype and allele frequency at D933G polymorphism site were significantly different between VSD group,TOF group and healthy control group（P=0.015,0.018;P=0.039,0.008）,and the relative risks for VSD and TOF in G allele carriers were higher than those in A allele carriers（VSD：OR=1.520,95%CI 1.020-2.266;TOF：OR=1.654,95%CI 1.137-2.406）.Conclusions The I495L and D933G polymorphisms of GLI1 gene are associated with CHD,and a person with C and G allele has higher risk with CHD.