title: Association between MTHFR gene polymorphisms and the risk of autism spectrum disorders: a meta-analysis.
abstract: Methylenetetrahydrofolate reductase (MTHFR) is essential for DNA biosynthesis and the epigenetic process of DNA methylation, and its gene polymorphisms have been implicated as risk factors for birth defects, neurological disorders, and cancers. However, reports on the association of MTHFR polymorphisms with autism spectrum disorders (ASD) are inconclusive. Therefore, we investigated the relationship of the MTHFR polymorphisms (C677T and A1298C) and the risk of ASD by meta-analysis. Up to December 2012, eight case-control studies involving 1672 patients with ASD and 6760 controls were included for meta-analysis. The results showed that the C677T polymorphism was associated with significantly increased ASD risk in all the comparison models [T vs. C allele (frequency of allele): odds ratio (OR) = 1.42, 95% confidence interval (CI): 1.09-1.85; CT vs. CC (heterozygote): OR = 1.48, 95% CI: 1.09-2.00; TT vs. CC (homozygote): OR = 1.86, 95% CI: 1.08-3.20; CT+TT vs. CC (dominant model): OR = 1.56, 95% CI: 1.12-2.18; and TT vs. CC+CT (recessive model): OR = 1.51, 95% CI: 1.02-2.22], whereas the A1298C polymorphism was found to be significantly associated with reduced ASD risk but only in a recessive model (CC vs. AA+AC: OR = 0.73, 95% CI: 0.56-0.97). In addition, we stratified the patient population based on whether they were from a country with food fortification of folic acid or not. The meta-analysis showed that the C677T polymorphism was found to be associated with ASD only in children from countries without food fortification. Our study indicated that the MTHFR C677T polymorphism contributes to increased ASD risk, and periconceptional folic acid may reduce ASD risk in those with MTHFR 677C>T polymorphism.
authors: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China; Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors: Danhua
authors: D
authors: Pu
authors: Yiping
authors: Y
authors: Shen
authors: Jie
authors: J
authors: Wu
mesh_terms: D016022:Case-Control Studies; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics* / Q000517:prevention & control; D003431:Cross-Cultural Comparison; D003906:Developing Countries; D044127:Epigenesis, Genetic / Q000235:genetics; D005492:Folic Acid / Q000008:administration & dosage; D005494:Folic Acid Deficiency / Q000150:complications / Q000235:genetics; D005527:Food, Fortified; D005787:Gene Frequency; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors
chemical_list: D005492:Folic Acid; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
keywords: autism spectrum disorders; folic acid; meta-analysis; methylenetetrahydrofolate reductase; polymorphism