Department of Zoology, University of Calcutta, Kolkata, West Bengal, India.
Department of Neonatology, Institute of Post Graduate Medical Education & Research, Kolkata, West Bengal, India.
Birth Defects Res. 2018 Aug 15;110(14):1129-1138. doi: 10.1002/bdr2.1365. Epub 2018 Aug 18.
Worldwide, Neural tube defects (NTDs) are considered as major clinical problems imposing a huge socio-economic burden for both affected individuals and their families. In India, the prevalence of Neural tube defects is significantly high. This study aims to evaluate the association between genetic defects in folate metabolism pathway genes, mainly: Folate hydrolase 1 (FOLH1), Dihydrofolate reductase (DHFR) and Methylenetetrahydrofolate reductase (MTHFR) and neural tube defects from eastern India.
We enrolled 62 consecutive mothers with NTDs foetuses as cases and their corresponding age matched 73 mothers with healthy babies as controls (genetic power has been calculated). Four single nucleotide polymorphisms (FOLH1: rs202676, DHFR: rs70991108, MTHFR: rs1801133 and rs1801131) have been amplified by polymerase chain reaction (PCR) and sequenced. Statistical analysis has been undertaken to find out association with NTDs.
Genotype and allele frequency analysis of these SNPs revealed that, rs1801133 (p.Ala222Val) was significantly associated with NTDs risk (p value = 0.028; odds ratio-2.31; 95% CI 1.08-4.93), whereas rs202676 (p.Tyr60His) showed protective role (p value = 0.0066; odds ratio-0.11; 95% CI 0.01-0.86). Serum homocysteine (Hcy) concentration was respectively higher in subjects carrying 222Ala/Val and 222Val/Val alleles (p value = 0.009; p value ≤ 0.0001).
In conclusion, it can be stated that, rs1801133 was associated with neural tube defects risk in patients from the eastern part of India and it might be counted as a molecular marker for evaluating the susceptibility of NTDs.
神经管缺陷（NTDs）在全球范围内被视为重大临床问题，给患者及其家庭带来了巨大的社会经济负担。在印度，神经管缺陷的患病率很高。本研究旨在评估叶酸代谢途径基因（主要是叶酸水解酶 1 [FOLH1]、二氢叶酸还原酶 [DHFR] 和亚甲基四氢叶酸还原酶 [MTHFR]）中的遗传缺陷与印度东部神经管缺陷之间的关联。
我们招募了 62 名连续患有 NTDs 胎儿的母亲作为病例，以及 73 名年龄匹配的母亲作为对照（已计算遗传力）。通过聚合酶链反应（PCR）扩增并测序了四个单核苷酸多态性（FOLH1：rs202676、DHFR：rs70991108、MTHFR：rs1801133 和 rs1801131）。进行了统计分析以找出与 NTDs 的关联。
这些 SNP 的基因型和等位基因频率分析表明，rs1801133（p.Ala222Val）与 NTDs 风险显著相关（p 值=0.028；优势比-2.31；95%置信区间 1.08-4.93），而 rs202676（p.Tyr60His）显示出保护作用（p 值=0.0066；优势比-0.11；95%置信区间 0.01-0.86）。携带 222Ala/Val 和 222Val/Val 等位基因的受试者的血清同型半胱氨酸（Hcy）浓度分别较高（p 值=0.009；p 值≤0.0001）。
总之，可以说 rs1801133 与印度东部地区患者的神经管缺陷风险相关，它可以作为评估 NTDs 易感性的分子标志物。
