Goldmuntz Elizabeth, Woyciechowski Stacy, Renstrom Daniel, Lupo Philip J, Mitchell Laura E
Division of Cardiology, Department of Pediatrics, The Children's Hospital of Philadelphia, PA 19104-4318, USA.
Circ Cardiovasc Genet. 2008 Dec;1(2):126-32. doi: 10.1161/CIRCGENETICS.108.796342. Epub 2008 Dec 9.
Although congenital heart defects (CHD) are the most common and serious group of birth defects, relatively little is known about the causes of these conditions and there are no established prevention strategies. There is evidence suggesting that the risk of CHD in general, and conotruncal and ventricular septal defects in particular, may be related to maternal folate status as well as genetic variants in folate-related genes. However, efforts to establish the relationships between these factors and CHD risk have been hampered by a number of factors including small study sample sizes and phenotypic heterogeneity.
The present study examined the relationships between variation in 9 folate-related genes and a subset of CHD phenotypes (ie, conotruncal defects, perimembranous and malalignment type ventricular septal defects, and isolated aortic arch anomalies) in a cohort of >700 case-parent triads. Further, both maternal and embryonic genetic effects were considered. Analyses of the study data confirmed an earlier reported association between embryonic genotype for MTHFR A1298C and disease risk (unadjusted P=0.002).
These results represent the most comprehensive and powerful analysis of the relationship between CHD and folate-related genes reported to date, and provide additional evidence that, similar to neural tube defects, this subset of CHD is folate related.
尽管先天性心脏病（CHD）是最常见且最严重的一组出生缺陷，但对于这些疾病的病因了解相对较少，且尚无既定的预防策略。有证据表明，一般CHD的风险，尤其是圆锥干和室间隔缺损的风险，可能与母亲的叶酸状态以及叶酸相关基因的遗传变异有关。然而，由于包括研究样本量小和表型异质性等多种因素，确定这些因素与CHD风险之间关系的努力受到了阻碍。
本研究在一个由700多个病例-父母三联体组成的队列中，研究了9个叶酸相关基因的变异与CHD表型子集（即圆锥干缺损、膜周型和对位不良型室间隔缺损以及孤立性主动脉弓异常）之间的关系。此外，还考虑了母亲和胚胎的遗传效应。对研究数据的分析证实了先前报道的MTHFR A1298C胚胎基因型与疾病风险之间的关联（未校正P = 0.002）。
这些结果代表了迄今为止报道的关于CHD与叶酸相关基因关系的最全面、最有力的分析，并提供了额外的证据，表明与神经管缺陷类似，这一CHD子集与叶酸有关。
