• Corpus ID: 51825986

Association of MTHFR Gene Variants with Autism

@inproceedings{Boris2004AssociationOM,
  title={Association of MTHFR Gene Variants with Autism},
  author={Marvin Boris and Allan Goldblatt and Joseph A. Galanko and S. Jill James},
  year={2004}
}

• M. Boris, A. Goldblatt, +1 author S. J. James
• Published 2004
• Biology, Medicine

Autism is a complex neurodevelopment disorder with numerous possible genetic and environmental influences. We retrospectively examined the laboratory data of 168 children sequentially referred to our facility with a confirmed diagnosis of autism or pervasive developmental disabilities (PDD). Since folate and methylation (single carbon metabolism) are vital in neurological development, we routinely screened children for the common mutations of the methylenetetrahydrofolate reductase gene (MTHFR), which regulates this pathway. All children had polymerase chain reaction (PCR) DNA evaluation to determine the frequency of the 677 and 1298 common polymorphisms in the MTHFR gene. We observed a significantly increased frequency of the homozygous mutation 677CT allele (TT): 23% in the autistic children compared to 11% in the control population ( <0.0001). Additionally, the heterozygous 677CT allele (CT) was present in 56% of the autistic children compared to 41% in the control population ( <0.0001). Somewhat paradoxically, the normal 1298AA allele was significantly higher in the autistic group, 55%, compared to the controls, 44% ( <0.05). Despite the increased frequency of normal 1298AA alleles, the compound 677CT/1298AC heterozygous mutations were more prevalent in the autistic population, 25%, than in controls, 15% ( =0.01). Overall, the data show an increased risk of autism spectrum disorder (ASD) associated with common mutations affecting the folate/methylation cycle. These associations by themselves may provide a partial explanation for a subgroup of children genomically at risk for ASD disorders. Increased folinic acid during pregnancy and early development may offset the genomic risk factors, and this deserves further study. Further, since folate-dependent methylation provides, in part, the methyl group for inactivation of monoamine neurotransmitters via the catecholamine-O-methyltransferase (COMT) system, this observation may help to further differentiate subtypes within the broad phenotype of ASD. A search for additional genomic and environmental risk factors should be undertaken. In particular, the methylation/transsulfation and COMT pathways should be investigated. P