Harisha Poomagame Narasimhamurthy, Devi B Indira, Christopher Rita, Kruthika-Vinod Tumkur Puttasiddhappa
Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India.
J Neurosurg Pediatr. 2010 Oct;6(4):364-7. doi: 10.3171/2010.8.PEDS1072.
Neural tube defects (NTDs) are among the most common congenital malformations worldwide. Their etiology and exact mechanisms of development are incompletely understood. Many enzymes involved in folate metabolism and the genes encoding these enzymes have been studied as candidates in their etiology. A mutation in the methylenetetrahydrofolate reductase (MTHFR) gene--a C-->T transition at nucleotide 677--is one among them. The mutation results in substitution of alanine by valine at a functionally important site in the enzyme. It has been shown to be a risk factor for development of NTDs in certain populations. The present study was conducted to evaluate the role of MTHFR 677 C-->T mutation as a risk factor for NTD in the South Indian population and to determine the relative importance of the genotypes in the affected child and its mother.
Blood samples were collected from the test and the control groups. The test group consisted of children with NTDs and their mothers, while the control group consisted of apparently healthy controls. MTHFR C677T polymorphism in the 3 groups was determined by polymerase chain reaction and restriction fragment length polymorphism studies. Comparison of polymorphism in the 3 groups was using the chi-square test.
There was a significant difference in the prevalence of MTHFR 677 C-->T mutation among the 3 groups (p = 0.002). The risk conferred by the TT genotype in the child was statistically significant (OR 12.625, 95% CI 1.430-111.465). In the mothers, however, although there was an increased prevalence of the mutation compared with the control individuals, the difference was not statistically significant (p = 0.152).
The MTHFR 677TT genotype is considered to be a definite risk factor for development of NTDs. It is the TT genotype status of the developing embryo, rather than the TT genotype status of its mother, that is the critical genetic determinant of MTHFR-related NTD risk.
神经管缺陷（NTDs）是全球最常见的先天性畸形之一。其病因及确切的发育机制尚未完全明确。许多参与叶酸代谢的酶以及编码这些酶的基因已作为其病因的候选因素进行了研究。亚甲基四氢叶酸还原酶（MTHFR）基因的一个突变——核苷酸677处的C→T转换——就是其中之一。该突变导致酶中一个功能重要位点的丙氨酸被缬氨酸取代。在某些人群中，它已被证明是神经管缺陷发生的一个危险因素。本研究旨在评估MTHFR 677 C→T突变作为南印度人群神经管缺陷危险因素的作用，并确定基因型在患病儿童及其母亲中的相对重要性。
从试验组和对照组采集血样。试验组由患有神经管缺陷的儿童及其母亲组成，而对照组由明显健康的对照者组成。通过聚合酶链反应和限制性片段长度多态性研究确定三组中的MTHFR C677T多态性。三组多态性的比较采用卡方检验。
三组中MTHFR 677 C→T突变的患病率存在显著差异（p = 0.002）。儿童中TT基因型带来的风险具有统计学意义（OR 12.625，95% CI 1.430 - 111.465）。然而，在母亲中，尽管与对照个体相比突变患病率有所增加，但差异无统计学意义（p = 0.152）。
MTHFR 677TT基因型被认为是神经管缺陷发生的一个明确危险因素。是发育中胚胎的TT基因型状态，而非其母亲的TT基因型状态，是MTHFR相关神经管缺陷风险的关键遗传决定因素。
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