{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T19:49:17Z","timestamp":1792439357400,"version":"4.5.0"},"reference-count":32,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,5,7]],"date-time":"2013-05-07T00:00:00Z","timestamp":1367884800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Autism Research"],"published-print":{"date-parts":[[2013,10]]},"abstract":"\n Methylenetetrahydrofolate reductase (\n MTHFR<\/jats:styled-content>\n ) is essential for\n DNA<\/jats:styled-content>\n biosynthesis and the epigenetic process of\n DNA<\/jats:styled-content>\n methylation, and its gene polymorphisms have been implicated as risk factors for birth defects, neurological disorders, and cancers. However, reports on the association of\n MTHFR<\/jats:styled-content>\n polymorphisms with autism spectrum disorders (\n ASD<\/jats:styled-content>\n ) are inconclusive. Therefore, we investigated the relationship of the\n MTHFR<\/jats:styled-content>\n polymorphisms (\n C677T<\/jats:styled-content>\n and\n A1298C<\/jats:styled-content>\n ) and the risk of\n ASD<\/jats:styled-content>\n by meta\u2010analysis. Up to\n D<\/jats:styled-content>\n ecember 2012, eight case\u2010control studies involving 1672 patients with\n ASD<\/jats:styled-content>\n and 6760 controls were included for meta\u2010analysis. The results showed that the\n C677T<\/jats:styled-content>\n polymorphism was associated with significantly increased\n ASD<\/jats:styled-content>\n risk in all the comparison models [\n T<\/jats:styled-content>\n vs.\n C<\/jats:styled-content>\n allele (frequency of allele): odds ratio (\n OR<\/jats:styled-content>\n )\u2009=\u20091.42, 95% confidence interval (\n CI<\/jats:styled-content>\n ): 1.09\u20131.85;\n CT<\/jats:styled-content>\n vs.\n CC<\/jats:styled-content>\n (heterozygote):\n OR<\/jats:styled-content>\n \u2009=\u20091.48, 95%\n CI<\/jats:styled-content>\n : 1.09\u20132.00;\n TT<\/jats:styled-content>\n vs.\n CC<\/jats:styled-content>\n (homozygote):\n OR<\/jats:styled-content>\n \u2009=\u20091.86, 95%\n CI<\/jats:styled-content>\n : 1.08\u20133.20;\n CT<\/jats:styled-content>\n +\n TT<\/jats:styled-content>\n vs.\n CC<\/jats:styled-content>\n (dominant model):\n OR<\/jats:styled-content>\n \u2009=\u20091.56, 95%\n CI<\/jats:styled-content>\n : 1.12\u20132.18; and\n TT<\/jats:styled-content>\n vs.\n CC<\/jats:styled-content>\n +\n CT<\/jats:styled-content>\n (recessive model):\n OR<\/jats:styled-content>\n \u2009=\u20091.51, 95%\n CI<\/jats:styled-content>\n : 1.02\u20132.22], whereas the A1298C polymorphism was found to be significantly associated with reduced\n ASD<\/jats:styled-content>\n risk but only in a recessive model (\n CC<\/jats:styled-content>\n vs.\n AA<\/jats:styled-content>\n +\n AC<\/jats:styled-content>\n :\n OR<\/jats:styled-content>\n \u2009=\u20090.73, 95%\n CI<\/jats:styled-content>\n : 0.56\u20130.97). 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\u2010analysis showed that the\n C677T<\/jats:styled-content>\n polymorphism was found to be associated with\n ASD<\/jats:styled-content>\n only in children from countries without food fortification. Our study indicated that the\n MTHFR C677T<\/jats:styled-content>\n polymorphism contributes to increased\n ASD<\/jats:styled-content>\n risk, and periconceptional folic acid may reduce\n ASD<\/jats:styled-content>\n risk in those with\n MTHFR 677C<\/jats:styled-content>\n >\n T<\/jats:styled-content>\n polymorphism.\n \n Autism Res<\/jats:bold>\n 2013, \u25cf\u25cf: \u25cf\u25cf\u2013\u25cf\u25cf\n <\/jats:italic>\n . \u00a9 2013 International Society for Autism Research, Wiley Periodicals, Inc.\n <\/jats:p>","DOI":"10.1002\/aur.1300","type":"journal-article","created":{"date-parts":[[2013,5,7]],"date-time":"2013-05-07T19:38:05Z","timestamp":1367955485000},"page":"384-392","source":"Crossref","is-referenced-by-count":114,"title":["Association between\n MTHFR<\/scp>\n Gene Polymorphisms and the Risk of Autism Spectrum Disorders: A\n M<\/scp>\n eta\u2010Analysis"],"prefix":"10.1002","volume":"6","author":[{"given":"Danhua","family":"Pu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine Nanjing Medical University Nanjing Jiangsu China"},{"name":"Department of Obstetrics and Gynecology The First Affiliated Hospital of Nanjing Medical University Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiping","family":"Shen","sequence":"additional","affiliation":[{"name":"Shanghai Children's Medical Center Jiaotong University School of Medicine Shanghai China"},{"name":"Departments of Laboratory Medicine and Pathology Boston Children's Hospital and Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine Nanjing Medical University Nanjing Jiangsu China"},{"name":"Department of Obstetrics and Gynecology The First Affiliated Hospital of Nanjing Medical University Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,5,7]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1089\/gtmb.2009.0019"},{"key":"e_1_2_5_3_1","first-page":"547","article-title":"Hyperhomocysteinemia among Omani autistic children: A case\u2010control study","volume":"58","author":"Ali A.","year":"2011","journal-title":"Acta Biochimica Polonica"},{"key":"e_1_2_5_4_1","first-page":"1","article-title":"Prevalence of autism spectrum disorders\u2014Autism and Developmental Disabilities Monitoring Network, 14 sites, United States, 2008","volume":"61","author":"Autism and Developmental Disabilities Monitoring Network Surveillance Year 2008 Principal Investigators; 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