COMT和MTHFR基因单体型及其血浆蛋白的表达与神经管畸形的相关性研究

项目名称： COMT和MTHFR基因单体型及其血浆蛋白的表达与神经管畸形的相关性研究

项目编号： No.81202265

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 预防医学、地方病学、职业病学、放射医学

项目作者： 刘菊芬

作者单位： 北京大学

项目金额： 23万元

中文摘要： 本课题组前期研究发现孕前及孕早期饮茶增加生育神经管畸形（NTDs）患儿的风险，推测茶叶中活性物质儿茶酚影响叶酸的代谢可能与儿茶酚胺氧位甲基转移酶（COMT）和5,10-亚甲基四氢叶酸还原酶（MTHFR）的基因多态性有关。本课题拟通过分析已收集到的600对病例对照（病例组为生育NTDs患儿的母亲，对照组为同期生育正常儿的母亲）的调查问卷和生物标本信息（血液和胎盘），通过检测COMT和MTHFR基因的多态性并构建单体型，同时测定血浆中COMT和MTHFR的蛋白表达、血浆和胎盘中重金属含量，分析环境因素（饮茶、重金属）和遗传因素（COMT和MTHFR多态性）的交互作用对NTDs发生的影响。该研究对于进一步阐明NTDs的发病机制和确定筛选高危人群或易感个体的分子标志物具有理论意义，从而为实施目标明确的个体预防、制定基于人群的预防干预措施提供理论依据。

中文关键词： 儿茶酚胺氧位甲基转移酶；5;10－亚甲基四氢叶酸还原酶；多态性；神经管畸形；基因-环境交互作用

英文摘要： Our previous study have shown that daily tea drinking during the periconceptional period was associated with a 3-fold elevated risk of NTDs (neural tube defects, NTDs) in the study population of North China. The active compounds in tea are believed to be tea polyphenols (primarily catechins and gallocatechins). Due to the similarity in molecular structure to folic acid, tea polyphenols competitively inhibit dihydrofolate reductase (DHFR) in cellular folate metabolism pathways and hence to decrease availability of folate or impaired folate metabolism. Methylation catalyzed by catechol-Omethyl transferase (COMT) represents a major metabolic pathway for tea polyphenols. Since the metabolic pathways of COMT and MTHFR are interconnected, variations in methylenetetrahydrofolate reductase (MTHFR) and COMT have been associated with elevated homocysteine, a risk factor for NTDs. In the present case-control study (600 cases and 600 controls), we would investigate the association between COMT/MTHFR haplotypes and NTDs. Enzymatic activity in the protein level would be evaluated to test the relationship of the functional variation linked to COMT and MTHFR haplotypes and NTDs. Environmental factors, such as smoking/passive smoking, folate, tea drinking, pesticide, organic solvent, heavy metal and nutrition status, would be co

英文关键词： COMT；MTHFR；single nucleotide polymorphism；neural tube defects；gene–environment interaction