Abstract
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.
Highlights
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
Hardy-Weinberg equilibrium The genotype frequencies of the vast majority of single nucleotide polymorphisms (SNPs) accorded with Hardy-Weinberg equilibrium in the control group (P > 0.05), except for the following four loci: betaine-homocysteine methyltransferase (BHMT) rs7700970, methylenetetrahydrofolate reductase (MTHFR) rs2066470, Methionine synthasereductase (MTRR) rs1532268, and MTRR rs1802059
Genotype frequencies of various SNPs in cases and controls Because 4 SNPs did not conform to Hardy-Weinberg equilibrium, they were excluded from the statistical
Summary
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. NTDs are birth defects of the brain, spine, or spinal cord that occur because of the insufficient intake of folic acid in the early stages of pregnancy. In 1991, Anonymous et al first clued that periconceptional supplementation of folic acid was able to prevent the recurrence of NTDs [5], which was further confirmed by many other subsequent studies [6]. U.S Public Health Service recommended that all women of childbearing age should be take 400 μg folic acid per day from 4 weeks before impregnation through gestation week 12 in order to prevent first occurrence of a NTDs-affected pregnancy [7]
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