Long Jin, Lupo Philip J, Goldmuntz Elizabeth, Mitchell Laura E
Institute of Biosciences and Technology, Texas A&M University System Health Science Center, Houston, USA.
Birth Defects Res A Clin Mol Teratol. 2011 Oct;91(10):879-84. doi: 10.1002/bdra.22849. Epub 2011 Aug 24.
Genetic variation in the folate metabolic pathway may influence the risk of congenital heart defects. This study was undertaken to assess the associations between the inherited and maternal genotypes for variants in folate-related genes and the risk of a composite heart phenotype that included two component phenotypes: conotruncal heart defects (CTDs) and left-sided cardiac lesions (LSLs).
Nine folate-related gene variants were evaluated using data from 692 case-parent triads (CTD, n = 419; LSL, n = 273). Log-linear analyses were used to test for heterogeneity of the genotype-phenotype association across the two component phenotypes (i.e., CTD and LSLs) and, when there was no evidence of heterogeneity, to assess the associations of the maternal and inherited genotypes with the composite phenotype.
There was little evidence of heterogeneity of the genotype-phenotype association across the two component phenotypes or of an association between the genotypes and the composite phenotype. There was evidence of heterogeneity in the association of the maternal MTR A2756G genotype (p = 0.01) with CTDs and LSLs. However, further analyses suggested that the observed associations with the maternal MTR A2756G genotype might be confounded by parental imprinting effects.
Our analyses of these data provide little evidence that the folate-related gene variants evaluated in this study influence the risk of this composite congenital heart defect phenotype. However, larger and more comprehensive studies that evaluate parent-of-origin effects, as well as additional folate-related genes, are required to more fully explore the relation between folate and congenital heart defects.
叶酸代谢途径中的基因变异可能会影响先天性心脏缺陷的风险。本研究旨在评估叶酸相关基因变异的遗传和母体基因型与一种复合心脏表型风险之间的关联，该复合心脏表型包括两种组成表型：圆锥动脉干心脏缺陷（CTD）和左侧心脏病变（LSL）。
使用来自692个病例 - 父母三联体（CTD，n = 419；LSL，n = 273）的数据评估9种叶酸相关基因变异。采用对数线性分析来检验基因型 - 表型关联在两种组成表型（即CTD和LSL）之间的异质性，并且在没有异质性证据时，评估母体和遗传基因型与复合表型之间的关联。
几乎没有证据表明基因型 - 表型关联在两种组成表型之间存在异质性，也没有证据表明基因型与复合表型之间存在关联。有证据表明母体MTR A2756G基因型与CTD和LSL的关联存在异质性（p = 0.01）。然而，进一步分析表明，观察到的与母体MTR A2756G基因型的关联可能受到亲本印记效应的混淆。
我们对这些数据的分析几乎没有提供证据表明本研究中评估的叶酸相关基因变异会影响这种复合先天性心脏缺陷表型的风险。然而，需要进行更大规模和更全面的研究来评估亲本来源效应以及其他叶酸相关基因，以便更充分地探索叶酸与先天性心脏缺陷之间的关系。
