遗传变异及基因-环境交互作用与非综合征先天性心脏病的病例对照研究

The genetic and environmental factors contributing to congenital heart defects(CHD), and their pathogenesis are hot topics in the epidemiological studies for birth defects. One family-based case-control study and another simple case-control study will be used to investigate the relationship between gene mutations, single nucleotide polymorphisms(SNP), environmental factors and the risk of nonsyndromic CHD. The main contents are as follows：1)Gene mutation screening and SNP association study: Mutation screening and SNP genotyping will be carried out in selected candidate genes implicated in fetal heart development and folate-related metabolism. Then geneotype and haplotype risks for CHD, and gene-gene interaction will be explored with pathway-based strategy. 2) Gene-environment interaction study: In case-control family study,information of maternal environmental exposures before and during pregnancy will be collected through questionnaire survey. Data from above studies will be incorporated into logistic regression models to evaluate the gene-enviroment interaction, the independent and combined effects of interested factors on CHD risk, including mutations, SNPs and folate-metabolism-related environmental exposures. The results of our studies will be of great value to the molecular pathogenetic understanding and prevention of CHD.

先天性心脏病(CHD)的遗传和环境病因及其发病机制是出生缺陷流行病学研究的热点。本课题采用病例-对照家系及简单病例对照设计，探讨候选基因突变、单核苷酸多态（SNP）、环境因素和非综合征CHD的关系。主要内容1）：基因突变及SNP关联研究：从胚胎心脏发育基因及叶酸代谢基因中确定候选基因及SNP标记，基于基因通路开展突变检测和SNP关联研究，分析基因型及单倍体型风险、探讨基因-基因交互作用；2）基因-环境交互作用研究：在病例-对照家系研究中，问卷调查母亲孕前及孕期环境暴露因素情况，应用Logistic回归模型探讨基因突变、SNP、影响机体叶酸代谢的环境因素的独立效应和基因-环境交互作用。研究结果可进一步揭示CHD的分子病因，为疾病早期预防提供依据。