Association of neural tube defects with maternal alterations and genetic polymorphisms in one-carbon metabolic pathway

被引:25
作者
Cai, Chun-Quan [1 ,2 ]
Fang, Yu-Lian [3 ]
Shu, Jian-Bo [3 ]
Zhao, Lin-Sheng [4 ]
Zhang, Rui-Ping [5 ]
Cao, Li-Rong [6 ]
Wang, Yi-Zheng [6 ]
Zhi, Xiu-Fang [6 ]
Cui, Hua-Lei [7 ]
Shi, Ou-Yan [8 ]
Liu, Wei [5 ]
机构
[1] Tianjin Univ, Coll Management & Econ, 92 Weijin Rd, Tianjin 300072, Peoples R China
[2] Tianjin Childrens Hosp, Dept Neurosurg, 238 Longyan Rd, Tianjin 300134, Peoples R China
[3] Tianjin Childrens Hosp, Inst Pediat, 238 Longyan Rd, Tianjin 300134, Peoples R China
[4] Tianjin Childrens Hosp, Dept Pathol, 238 Longyan Rd, Tianjin 300134, Peoples R China
[5] Tianjin Childrens Hosp, Dept Pediat, 238 Longyan Rd, Tianjin 300134, Peoples R China
[6] Tianjin Med Univ, Grad Sch, 22 Qixiangtai Rd, Tianjin 300070, Peoples R China
[7] Tianjin Childrens Hosp, Dept Surg, 238 Longyan Rd, Tianjin 300134, Peoples R China
[8] Tianjin Med Univ, Sch Basic Med Sci, 22 Qixiangtai Rd, Tianjin 300070, Peoples R China
基金
中国国家自然科学基金;
关键词
Neural tube defects; One-carbon metabolism; Gene; Polymorphism; FOLIC-ACID; DNA METHYLATION; RISK; PREVENTION; REDUCTASE; INCREASE; MOTHERS; A2756G;
D O I
10.1186/s13052-019-0630-1
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
BackgroundNeural 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.MethodsWe 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.ResultsThere 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).ConclusionFolic acid deficiency, MTHFD1 rs2236225, MTHFR rs1801133, MTRR rs1801349 and RFC1 rs1051226 polymorphisms may be maternal risk factors of NTDs.
引用
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页数:7
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