Association between MTHFR gene polymorphisms and the risk of autism spectrum disorders: a meta-analysis. 2013

Danhua Pu, and Yiping Shen, and Jie Wu
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.

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.

UI MeSH Term Description Entries
D011110 Polymorphism, Genetic The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level. Gene Polymorphism,Genetic Polymorphism,Polymorphism (Genetics),Genetic Polymorphisms,Gene Polymorphisms,Polymorphism, Gene,Polymorphisms (Genetics),Polymorphisms, Gene,Polymorphisms, Genetic
D002648 Child A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL. Children
D002659 Child Development Disorders, Pervasive Severe distortions in the development of many basic psychological functions that are not normal for any stage in development. These distortions are manifested in sustained social impairment, speech abnormalities, and peculiar motor movements. Pervasive Child Development Disorders,Pervasive Development Disorders
D003431 Cross-Cultural Comparison Comparison of various psychological, sociological, or cultural factors in order to assess the similarities or diversities occurring in two or more different cultures or societies. Transcultural Studies,Comparison, Cross-Cultural,Comparisons, Cross-Cultural,Cross Cultural Comparison,Cross-Cultural Comparisons,Studies, Transcultural,Study, Transcultural,Transcultural Study
D003906 Developing Countries Countries in the process of change with economic growth, that is, an increase in production, per capita consumption, and income. The process of economic growth involves better utilization of natural and human resources, which results in a change in the social, political, and economic structures. LMICs,Less-Developed Countries,Low Income Countries,Low and Middle Income Countries,Lower-Middle-Income Country,Middle Income Countries,Third-World Countries,Under-Developed Countries,Developing Nations,Least Developed Countries,Less-Developed Nations,Third-World Nations,Under-Developed Nations,Countries, Middle Income,Countries, Third-World,Country, Least Developed,Country, Less-Developed,Country, Low Income,Country, Lower-Middle-Income,Country, Middle Income,Country, Third-World,Country, Under-Developed,Developed Country, Least,Developing Country,Developing Nation,Least Developed Country,Less Developed Countries,Less Developed Nations,Less-Developed Country,Less-Developed Nation,Low Income Country,Lower Middle Income Country,Lower-Middle-Income Countries,Middle Income Country,Nation, Less-Developed,Nation, Third-World,Nation, Under-Developed,Third World Countries,Third World Nations,Third-World Country,Third-World Nation,Under Developed Countries,Under Developed Nations,Under-Developed Country,Under-Developed Nation
D005492 Folic Acid A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses (POACEAE). Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. Pteroylglutamic Acid,Vitamin M,Folacin,Folate,Folic Acid, (D)-Isomer,Folic Acid, (DL)-Isomer,Folic Acid, Calcium Salt (1:1),Folic Acid, Monopotassium Salt,Folic Acid, Monosodium Salt,Folic Acid, Potassium Salt,Folic Acid, Sodium Salt,Folvite,Vitamin B9,B9, Vitamin
D005494 Folic Acid Deficiency A nutritional condition produced by a deficiency of FOLIC ACID in the diet. Many plant and animal tissues contain folic acid, abundant in green leafy vegetables, yeast, liver, and mushrooms but destroyed by long-term cooking. Alcohol interferes with its intermediate metabolism and absorption. Folic acid deficiency may develop in long-term anticonvulsant therapy or with use of oral contraceptives. This deficiency causes anemia, macrocytic anemia, and megaloblastic anemia. It is indistinguishable from vitamin B 12 deficiency in peripheral blood and bone marrow findings, but the neurologic lesions seen in B 12 deficiency do not occur. (Merck Manual, 16th ed) Deficiency, Folic Acid,Acid Deficiencies, Folic,Acid Deficiency, Folic,Deficiencies, Folic Acid,Folic Acid Deficiencies
D005527 Food, Fortified Any food that has been supplemented with essential NUTRIENTS either in quantities that are greater than those normally present, or which are not found in the food typically. Fortified food also includes food enriched by adding various nutrients to compensate for those removed by refinement or processing. (Modified from Segen, Dictionary of Modern Medicine, 1992). Enriched Food,Food, Supplemented,Enriched Foods,Food, Enriched,Foods, Enriched,Foods, Fortified,Foods, Supplemented,Fortified Food,Fortified Foods,Supplemented Food,Supplemented Foods
D005787 Gene Frequency The proportion of one particular in the total of all ALLELES for one genetic locus in a breeding POPULATION. Allele Frequency,Genetic Equilibrium,Equilibrium, Genetic,Allele Frequencies,Frequencies, Allele,Frequencies, Gene,Frequency, Allele,Frequency, Gene,Gene Frequencies
D005838 Genotype The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS. Genogroup,Genogroups,Genotypes

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