MTHFR 677C→T and 1298A→C polymorphisms:: Evaluation of maternal genotypic risk and association with level of neural tube defect
MTHFR 677C→T and 1298A→C polymorphisms:: Evaluation of maternal genotypic risk and association with level of neural tube defect
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DOI：
10.1159/000096735
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发表时间：
2007-01-01
影响因子：
2.1
通讯作者：
Agarwal, Sarita
中科院分区：
文献类型：
--
作者：
Dalal, Ashwin;Pradhan, Mandakini;Agarwal, Sarita
背景：神经管缺陷（NTDs）是常见的出生缺陷（1 / 1000）导致显著的发病率和死亡率。围孕期补充叶酸有助于预防70%的被忽视热带病。最近，叶酸通路基因编码酶的多态性被认为与NTDs的病因有关。由于神经管关闭发生在多个部位，不同部位缺陷的病因可能不同，这解释了叶酸补充不能预防所有神经管缺陷的原因。方法：采用聚合酶链反应和限制性内切酶对亚甲基四氢叶酸还原酶多态性进行分子分析。我们研究了这些多态性在母亲与先前患有NTD的孩子之间的关联，并通过基于缺陷水平的分层进一步细化了风险。结果：677C -> T纯合子在既往患儿中出现的频率高于对照组（OR=1.6 (0.38 ~ 6.7), 95% CI, p= 0.72），但差异无统计学意义。与对照组相比，前一个孩子有“较低”类型缺陷的母亲的T等位基因频率有显著差异（OR=2.15 (1.13-4.1), 95% CI, p=0.02）。我们没有发现1298A -> C多态性与NTDs水平有显著关联。结论：我们得出结论，在北印度人群中，MTHFR基因的677C -> T等位基因可能与低类型NTD的发生有关。这表明热稳定性MTHFR在神经管闭合的不同部位的不同作用。版权所有(c) 2007 S. Karger AG，巴塞尔。
Background: Neural tube defects (NTDs) are common birth defects ( 1 in 1,000) leading to significant morbidity and mortality. Periconceptional folic acid supplementation helps in prevention of 70% of NTDs. Recently, polymorphisms in genes encoding enzymes of the folate pathway have been implicated in causation of NTDs. Since the closure of neural tube occurs at multiple sites, the etiology of defect at different sites may be different-which explains the failure of folic acid supplementation to prevent all NTDs. Methods: Molecular analysis of methylenetetrahydrofolate reductase polymorphisms was carried out using polymerase chain reaction and restriction enzyme digestion. We studied the association of these polymorphisms in mothers with a previous child with NTD and further refined the risk by stratification based on level of defect. Results: The frequency of 677C -> T homozygotes was higher in mothers with a previous child with NTD than the controls (OR=1.6 (0.38-6.7), 95% CI, p= 0.72) but the difference was statistically insignificant. There was a significant difference in frequency of T alleles among mothers with a previous child with a 'lower' type of defect compared to controls (OR=2.15 (1.13-4.1), 95% CI, p=0.02). We did not find any significant association of 1298A -> C polymorphism with the level of NTDs. Conclusions: We conclude that in the North Indian population, the 677C -> T allele of the MTHFR gene may be associated with the occurrence of a lower type of NTD. This points towards the differential role of thermolabile MTHFR at different sites of neural tube closure. Copyright (c) 2007 S. Karger AG, Basel.