母亲胱硫醚β-合酶基因多态性与子代先心病及亚型的关联研究

Association of Maternal CystathionineβSynthase Gene Polymorphisms with Congenital Heart Disease and its Subtypes in Offspring

目的探讨母亲胱硫醚β-合成酶(cystathionineβsynthase,CBS)基因多态性与子代先心病(congenital heart disease,CHD)及其亚型的关联,为CHD遗传易感标志物的研究提供流行病学依据。方法以464例单纯CHD患儿母亲为病例组,504例正常儿童母亲为对照组,开展病例对照研究。通过问卷调查,收集研究对象的基本信息。完成调查问卷后,采集5ml血液,用于CBS基因多态性的检测。利用多因素logistic回归模型评估CBS基因多态性与CHD及亚型的关联;利用Haploview 4.2软件的四配子法构建单倍型,评估单倍型与CHD的关联;利用广义多因子降维法(GMDR)分析基因-基因交互作用与CHD的关联。结果多因素logistic回归分析结果显示,母亲CBS基因位点rs2851391和rs234714的多态性与子代CHD及其两种亚型(ASD和PDA)的发病存在关联;且经FDR调整后,关联仍然具有统计学意义(Q_(FDR)<0.05)。5个SNP位点均与VSD的发生无关(Q_(FDR)>0.05)。GMDR分析结果显示,5个SNP位点的基因-基因交互作用模型与子代CHD的发生无关(P>0.05)。rs1051319和rs2851391位点构成的单倍型G-T可能与子代CHD的发生有关(Q_(FDR)<0.05)。结论母亲CBS基因多态性与子代CHD、ASD和PDA的发生有关,CBS基因位点构成的单倍型(G-T)也与子代CHD的发生有关。

Objective To investigate the association of polymorphism of maternal cystathionineβsynthase(CBS)gene with congenital heart disease(CHD)and its subtypes in the offspring,and provide an epidemiological basis for the study of genetic susceptibility markers for CHD.Methods A case-control study was carried out with 464 mothers of children with CHD as the case group and 504 mothers of normal children as the control group.Basic information about the research objects was collected through questionnaire surveys.After completing the questionnaire,venous blood samples(5 mL)were collected from the research subjects for the detection of CBS gene polymorphism.Multivariate logistic regression model was used to evaluate the association of CBS gene polymorphism with CHD and subtypes.Haploview 4.2 was used to construct haplotype and investigate the association between haplotypes and CHD by the four gametes method.The association of gene-gene interaction with CHD was evaluated by generalized multifactor dimensionality reduction(GMDR)method.Results Multivariate logistic regression analysis showed that the maternal CBS gene locus rs2851391 and rs234714 polymorphism are associated with the onset of CHD and its two subtypes(ASD and PDA)in the offspring.And after FDR adjustment,the association is still statistically significant(Q_(FDR)<0.05).the 5 SNP loci are not related to the occurrence of VSD(Q_(FDR)>0.05).GMDR analysis showed that the gene-gene interaction model of 5 SNP loci had nothing to do with the occurrence of CHD in the offspring(P>0.05).The haplotype G-T(Q_(FDR)<0.05)formed by rs1051319 and rs2851391 may be related to the occurrence of CHD in offspring.Conclusion Maternal CBS gene polymorphism is associated with the occurrence of CHD,ASD and PDA in the offspring.The haplotype(G-T)formed by CBS gene locus is also associated with the occurrence of CHD in offspring.