Confirmation of the R653Q polymorphism of the trifunctional C1-synthase enzyme as a maternal risk for neural tube defects in the Irish population
Confirmation of the R653Q polymorphism of the trifunctional C1-synthase enzyme as a maternal risk for neural tube defects in the Irish population
复制标题
DOI：
10.1038/sj.ejhg.5201603
复制
发表时间：
2006-06-01
影响因子：
5.2
通讯作者：
Scott, John M.
中科院分区：
文献类型：
--
作者：
Parle-McDermott, Anne;Kirke, Peadar N.;Scott, John M.
神经管缺陷（NTDs）的风险是已知的，有一个显着的遗传成分，可以通过NTD患者和/或母亲的基因型。补充叶酸在NTD预防中的成功使人们关注叶酸相关基因的多态性。我们先前鉴定了三功能酶MTHFD 1（亚甲基四氢叶酸脱氢酶、亚甲基四氢叶酸环水解酶、甲酰四氢叶酸合成酶;通常称为“C1脱氢酶”）的1958 G> A（R653 Q）多态性作为NTD的母体风险，但这种关联仍有待于在单独的研究中验证以排除偶然发现。为了排除这种可能性，我们对来自同一爱尔兰人群的有NTD影响妊娠史的母亲进行了基因分型。在该样本中，NTD病例（n = 245）的1958 AA纯合子母亲明显多于对照组（n = 770）。风险的方向和程度（比值比1.49（1.07 - 2.09），P = 0.019）与我们早期的发现一致。MTHFD 1基因的测序显示，这种关联不是由编码区内的另一种常见变体驱动的。我们已经确定MTHFD 1 1958 G> A多态性在影响爱尔兰人群中母亲患NTD影响妊娠的风险方面具有重要作用。
The risk of neural tube defects (NTDs) is known to have a significant genetic component that could act through either the NTD patient and/ or maternal genotype. The success of folic acid supplementation in NTD prevention has focused attention on polymorphisms within folate-related genes. We previously identified the 1958G > A (R653Q) polymorphism of the trifunctional enzyme MTHFD1 ( methylenetetrahydrofolate-dehydrogenase, methenyltetrahydrofolate- cyclohydrolase, formyltetrahydrofolate synthetase; often referred to as 'C1 synthase') as a maternal risk for NTDs, but this association remains to be verified in a separate study to rule out a chance finding. To exclude this possibility, we genotyped an independent sample of mothers with a history of an NTD-affected pregnancy derived from the same Irish population. In this sample there was a significant excess of 1958AA homozygote mothers of NTD cases (n = 245) compared to controls ( n 770). The direction and magnitude of risk ( odds ratio 1.49 (1.07 - 2.09), P = 0.019) is consistent with our earlier finding. Sequencing of the MTHFD1 gene revealed that this association is not being driven by another common variant within the coding region. We have established that the MTHFD1 1958G > A polymorphism has a significant role in influencing a mother's risk of having an NTD- affected pregnancy in the Irish population.