Page 1 of 3 Licensee OAPL (UK) 2014. Creative Commons Attribution License (CC-BY) FOR CITATION PURPOSES: Samtani R. Epigenetics and autism: Insights for future research. OA Autism 2014 Jul 18;2(2):14. Critical review Competing interests: None declared. Conflict of interests: None declared. All authors contributed to conception and design, manuscript preparation, read and approved the final manuscript. All authors abide by the Association for Medical Ethics (AME) ethical rules of disclosure. Diagnosis Advancements Epigenetics and autism: Insights for future research R Samtani 1* Abstract Introduction Autism is approaching the numbers of an epidemic. Past efforts have focused on identifying the genetic basis of Autism Spectrum disorders with minimal success. Recently, a lot of work is being carried out in Epigenetics, Nutrigenetics in order to analyse the cause of Autism Spectrum Disorders. The present paper reviews the various studies being conducted in this domain and provides recommendations for further studies in this area. Conclusion As DNA methylation marks are reversible and dynamic, there is a possibility of reversing these marks by dietary intake of methyl donors and pharmacological agents which can therefore help in diagnosis and eventual treatment of autism. Introduction Autism (autism spectrum disorders) is a complex, strongly genetically influenced, and behaviourally defined disorder of the immature brain associated with very uneven intellectual abilities. Its many causes, robust heritability with epigenetic influences and a wide range of severity means that there is no symptom, no pathology, imaging, electroencephalography, or other biologic feature, and no biologic treatment that is universal or diagnostic of this developmental syndrome. Autism is approaching the numbers of an epidemic. The figures are staggering in the 1960s; four in 10,000 children have had autism. Today, according to Autism Speaks, an organization dedicated to facilitating global research into the causes, treatments and an eventual cure for autism, one in every 110 children is diagnosed with autism, making it more common than childhood cancer, juvenile diabetes and paediatric AIDS combined. U.S. government statistics suggest that the prevalence rate of autism is increasing 10-17% annually (Autism Society estimate based on 2003 US state educational data). Past efforts have focused on identifying the genetic basis of Autism Spectrum disorders with minimal success. Recently, a lot of work is being carried out in Epigenetics, Nutrigenetics in order to analyse the cause of Autism Spectrum Disorders. The present paper reviews the various studies being conducted in this domain and will provide recommendations for further studies in this area. Discussion Genetic and Epigenetic basis of Autism Autism demonstrates robust heritability suggesting a strong genetic component. However, calculations of genetic heritability are based on a large extent on monozygotic twin studies. Monozygotic twins share not only genes but also environments and a common germ line DNA methylation pattern 1 . It is therefore possible that the genetic contribution to autism has been overestimated and the epigenetic component underestimated. Several studies point to an epigenetic basis for autism. RETT syndrome, a mental retardation disorder that is similar in certain aspects with autistic spectrum disorders, is caused by a deficiency in MeCP2, an epigenetic protein that binds methylated DNA and has several roles in interpretation of the DNA methylation pattern as well as in controlling DNA methylation states 2 . Alterations in DNA methylation in the promoter of MeCP2 were shown in autistic brains linking autism, DNA methylation and MeCP2 3 . Epigenetic variation is predicted to be a potentially more common cause of dysregulation to synaptic pathways 3 . A compelling reason to investigate epigenetic mechanisms in idiopathic autism is that such modifications can be influenced by exposure to biological modulators and environmental factors. Epigenetics may thus mediate the interaction between genotype and intrinsic (biological) or extrinsic (environmental) factors contributing to ASDs. Of all the epigenetic modulations, DNA methylation has the most established role in-regulation of promoter activity and gene regulatory regions 4 . At least two mechanisms have been demonstrated for inhibition of gene activity by DNA methylation. A methyl group positioned in a recognition element for a transcriptional factor can block binding of the transcription factor to the promoter 5,6 . Alternatively, methylated DNA attracts methylated DNA binding proteins such as the Rett syndrome protein methyl-CpG binding protein 2 (MeCP2), which in turn recruit histone modification enzymes such as histone deacetylases (HDAC)s to the gene precipitating an inactive gene silencing chromatin configuration 7 . Nutritional modification of DNA methylation Nutritional modification of DNA methylation can have profound effects on phenotypic outcome of social animals. As normal activity of the methionine cycle metabolites is important for methylation, there has been a considerable effect of nutrients on DNA methylation. Folate, a water- soluble B vitamin, has been extensively studied for its effect on DNA methylation 8 because folate carries a methyl group and ultimately delivers that methyl group for the synthesis of AdoMet, the unique methyl donor for DNA methylation reactions. However, folate is not the sole *Corresponding author Email: rsamtani@amity.edu 1 Amity Institute of Anthropology, Amity University, India