van Beynum I M, den Heijer M, Blom H J, Kapusta L
Children's Heart Centre, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
QJM. 2007 Dec;100(12):743-53. doi: 10.1093/qjmed/hcm094. Epub 2007 Oct 26.
Periconceptional folic acid supplementation may protect against congenital heart defects (CHDs). Identification of candidate genes in folate metabolism has suggested that the 677C-->T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene may be particularly associated with the risk of CHDs.
To assess the relationship between MTHFR 677C-->T and CHDs by literature review and meta-analysis.
Studies were identified by searches of electronic literature for papers focussing on MTHFR 677C-->T and the risk of any type of CHD. Both case-control comparisons and transmission-disequilibrium tests (TDTs) in family-based designs were included.
We found 13 eligible studies. Of 10 case-control studies, four focused on the fetal polymorphism, two studied the maternal polymorphism, and a further four investigated both. Three further publications used a family-based association study to assess the effect of the T allele on cardiac development. Overall analysis yielded odds ratios of 1.3 (95%CI 0.97-1.73) and 1.2 (95%CI 0.83-1.74) for fetal and maternal MTHFR TT genotypes, respectively. TDTs revealed no association between fetal 677T allele and CHDs.
This relatively small meta-analysis found no substantial evidence of increased CHD risk in individuals with MTHFR 677CT and TT genotypes. Heterogeneity regarding population background, study design and type of heart defects complicates the pooling and comparison of the studies. The effect of modification by periconceptional folic acid intake should be taken into account. Further larger studies and well-defined phenotypic subcategory analyses are needed to decide whether the MTHFR 677C-->T polymorphism of the affected child and/or their mother is truly a risk factor for the development of CHDs.
孕期补充叶酸可能预防先天性心脏病（CHD）。叶酸代谢相关候选基因的鉴定表明，亚甲基四氢叶酸还原酶（MTHFR）基因的677C→T多态性可能与CHD风险特别相关。
通过文献综述和荟萃分析评估MTHFR 677C→T与CHD之间的关系。
通过检索电子文献来确定研究，搜索重点为MTHFR 677C→T与任何类型CHD风险的相关论文。纳入病例对照比较和基于家系设计的传递不平衡检验（TDT）。
我们找到13项符合条件的研究。在10项病例对照研究中，4项关注胎儿多态性，2项研究母亲多态性，另外4项同时研究两者。另有3篇出版物采用基于家系的关联研究来评估T等位基因对心脏发育的影响。总体分析得出，胎儿和母亲MTHFR TT基因型的优势比分别为1.3（95%CI 0.97 - 1.73）和1.2（95%CI 0.83 - 1.74）。TDT显示胎儿677T等位基因与CHD之间无关联。
这项规模相对较小荟萃分析未发现有充分证据表明MTHFR 677CT和TT基因型个体患CHD风险增加。人群背景、研究设计和心脏缺陷类型方面的异质性使研究的汇总和比较变得复杂。应考虑孕期叶酸摄入的修正作用。需要进一步开展更大规模的研究以及明确的表型亚类分析，以确定患病儿童和/或其母亲的MTHFR 677C→T多态性是否真的是CHD发生的风险因素。
