神经管缺陷与母体改变及一碳代谢途径中遗传多态性的关系。
Association of neural tube defects with maternal alterations and genetic polymorphisms in one-carbon metabolic pathway.
机构信息
College of Management and Economics, Tianjin University, No.92 Weijin Road, Tianjin, 300072, China.
Department of Neurosurgery, Tianjin Children's Hospital, No.238 Longyan Road, Beichen District, Tianjin, 300134, China.
出版信息
Ital J Pediatr. 2019 Mar 14;45(1):37. doi: 10.1186/s13052-019-0630-1.
BACKGROUND
Neural tube defects (NTDs) are birth defects of the brain, spine, or spinal cord invoked by the insufficient intake of folic acid in the early stages of pregnancy and have a complex etiology involving both genetic and environmental factors. So the study aimed to explore the association between alterations in maternal one-carbon metabolism and NTDs in the offspring.
METHODS
We conducted a case-control study to get a deeper insight into this association, as well as into the role of genetic polymorphisms. Plasma concentrations of folate, homocysteine (Hcy), S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) and genotypes and alleles distributions of 52 SNPs in 8 genes were compared for 61 women with NTDs-affected offspring and 61 women with healthy ones.
RESULTS
There were significant differences between groups with regard to plasma folate, SAM, SAH and SAM/SAH levels. Logistic regression results revealed a significant association between maternal plasma folate level and risk of NTDs in the offspring. For MTHFD1 rs2236225 polymorphism, mothers having GA genotype and A allele exhibited an increased risk of NTDs in the offspring (OR = 2.600, 95%CI: 1.227-5.529; OR = 1.847, 95%CI: 1.047-3.259). For MTHFR rs1801133 polymorphism, mothers having TT and CT genotypes were more likely to affect NTDs in the offspring (OR = 4.105, 95%CI: 1.271-13.258; OR = 3.333, 95%CI: 1.068-10.400). Moreover, mothers carrying T allele had a higher risk of NTDs in the offspring (OR = 1.798, 95%CI: 1.070-3.021). For MTRR rs1801394 polymorphism, the frequency of G allele was significantly higher in cases than in controls (OR = 1.763, 95%CI: 1.023-3.036). Mothers with NTDs-affected children had higher AG genotype in RFC1 rs1051226 polymorphism than controls, manifesting an increased risk for NTDs (OR = 3.923, 95%CI: 1.361-11.308).
CONCLUSION
Folic acid deficiency, MTHFD1 rs2236225, MTHFR rs1801133, MTRR rs1801349 and RFC1 rs1051226 polymorphisms may be maternal risk factors of NTDs.
背景
神经管缺陷（NTDs）是由妊娠早期叶酸摄入不足引起的大脑、脊柱或脊髓的先天缺陷，其病因复杂，涉及遗传和环境因素。因此，本研究旨在探讨母体一碳代谢改变与后代 NTDs 之间的关系。
方法
我们进行了一项病例对照研究，以更深入地了解这种关联，以及遗传多态性的作用。比较了 61 名 NTDs 患儿母亲和 61 名健康母亲的血浆叶酸、同型半胱氨酸（Hcy）、S-腺苷甲硫氨酸（SAM）、S-腺苷同型半胱氨酸（SAH）浓度以及 8 个基因中 52 个 SNP 的基因型和等位基因分布。
结果
两组间血浆叶酸、SAM、SAH 和 SAM/SAH 水平存在显著差异。Logistic 回归结果显示，母体血浆叶酸水平与后代 NTDs 风险之间存在显著关联。对于 MTHFD1 rs2236225 多态性，GA 基因型和 A 等位基因的母亲发生 NTDs 的风险增加（OR=2.600，95%CI：1.227-5.529；OR=1.847，95%CI：1.047-3.259）。对于 MTHFR rs1801133 多态性，TT 和 CT 基因型的母亲更有可能影响后代的 NTDs（OR=4.105，95%CI：1.271-13.258；OR=3.333，95%CI：1.068-10.400）。此外，携带 T 等位基因的母亲发生 NTDs 的风险更高（OR=1.798，95%CI：1.070-3.021）。对于 MTRR rs1801394 多态性，病例组 G 等位基因频率明显高于对照组（OR=1.763，95%CI：1.023-3.036）。携带 RFC1 rs1051226 多态性的 AG 基因型的母亲所生孩子患有 NTDs 的风险高于对照组，表明 NTDs 的风险增加（OR=3.923，95%CI：1.361-11.308）。
结论
叶酸缺乏、MTHFD1 rs2236225、MTHFR rs1801133、MTRR rs1801349 和 RFC1 rs1051226 多态性可能是 NTDs 的母体危险因素。
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