The MTHFR 677C→T polymorphism and behaviors in children with autism: Exploratory genotype-phenotype correlations

Robin P. Goin-Kochel, Anne E. Porter, Sarika U. Peters, Marwan Shinawi, Trilochan Sahoo, Arthur L. Beaudet

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44 Scopus citations


New evidence suggests that autism may be associated with (a) varied behavioral responses to folate therapy and (b) metabolic anomalies, including those in folate metabolism, that contribute to hypomethylation of DNA. We hypothesized that children with autism who are homozygous for the MTHFR 677 T allele (TT) and, to a lesser extent those with the CT variant, would exhibit more behavioral problems and/or more severe problematic behaviors than homozygous wild-type (CC) individuals because of difficulties in effectively converting 5,10-MTHF to 5-MTHF. Data from the Autism Genetic Resource Exchange (AGRE) collection were analyzed for all children who met strict criteria for autism per the Autism Diagnostic Interview - Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) and who had been genotyped for the 677 C to T MTHFR polymorphism (n = 147). Chi-square tests, logistic regression, and oneway ANOVAs were used to determine whether differences existed among MTHFR genotypes for specific behaviors on the ADI-R and indices for level of functioning. Exploratory results indicated four behaviors from the ADI-R that were more common and problematic (95% CI) among those with at least one copy of the T allele as compared to homozygous wildtype individuals: direct gaze, current complex body movements, a history of self-injurious behavior, and current overactivity (ORs = 2.72, 2.33, 2.12, 2.47, respectively). No differences existed among genotypes for level of functioning as measured with the Peabody Picture Vocabulary Test - Third Edition, Ravens Colored Progressive Matrices, or the Vineland Adaptive Behavior Scales. Findings call for further investigation of the relationship between folate metabolism and problem behaviors among children with autism.

Original languageEnglish
Pages (from-to)98-108
Number of pages11
JournalAutism Research
Issue number2
StatePublished - Apr 2009


  • Clinical psychology
  • Epigenetics
  • Genetics
  • Regression


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