|Silentio! @ Wikipedia|
Based on an initial analysis of 5 pairs of participants - five diagnosed with autism, the other five being asymptomatic controls - drawn from a larger study population (n=131 pairs), researchers conducted a genome-wide study of venous blood samples for methylation variations in gene promoter regions and CpG islands using a method called MeDIP. Candidate genes (LASS3, PANX2, SLC15A4 and ENO2) which showed differential methylation patterns between the autism vs. control samples were selected for further investigation, after which ENO2 became the target gene for the study. It was then a case of verifying the methylation status of ENO2 (via BSP sequencing) in cases and controls of the larger participant groups followed by some analysis of the expression of ENO2 with regards to RNA levels and protein expression.
The results: "hypermethylation of a single gene, ENO2, may be associated with about 15 % of
autistic cases". All of the children with ENO2 hypermethylation had "significant language development disorder" which contrasted with the other children in the autism group who "had more or less spoken language" although I didn't note any specific language measure to be used in this trial. ENO2 RNA levels were "reduced by about 70% relative to that in controls" and ENO2 protein expression in the hypermethylated group "was about half of that of controls".
Ergo, "ENO2 expression may be a biomarker for a subset of autistic children".
OK first things first, CpG sites and DNA. Imagine if you will, that in amongst the very complicated genetic blueprint which guides things like eye colour or whether you've inherited that magnificent nose from dad or mum, there are islands of DNA which contain a particular sequence separated by phosphate: cytosine - phosphate - guanine (CpG). The cytsosine part of the CpG site can be methylated - the addition of a methyl group - to form 5-methylcytosine; methylation in this respect generally taken to mean gene silencing or at least a reduction in gene function which can then lead to decreased gene transcription and onwards less protein expression.
The Wang results basically plotted how from looking at the methylation status of the genome, a specific candidate gene showing something like a distinct methylation pattern in some cases of autism was followed through to see how said methylation affects gene function. It goes without saying that this was a very preliminary study and judging by the participant numbers needed in more traditional studies looking at structural changes to the genome (SNPs, CNVs et al) replication on a much grander scale (and looking at specific tissues) is absolutely implied before anyone gets too carried away. That also it's most probably autisms over autism together with the the principles of RDoC are other issues to be kept in mind.
Still, I don't want to take anything away from the Wang results and what they 'could' potentially mean in light of other research in this area. Whether or not ENO2 survives future replicative studies is to some extent secondary to the question of why this gene was hypermethylated in the first place? Does this suggest a role for some of the DNA methyltransferases in relation to autism? What about the mechanisms of methyl donation and the functions of things like S-Adenosyl methionine (SAMe) in that process? Lots of different layers of complexity to be added to our knowledge of the genome.
Music to close. Coldplay and Magic...
 Wang Y. et al. Hypermethylation of the enolase gene (ENO2) in autism. Eur J Pediatr. 2014 Apr 17.
Wang Y, Fang Y, Zhang F, Xu M, Zhang J, Yan J, Ju W, Brown WT, & Zhong N (2014). Hypermethylation of the enolase gene (ENO2) in autism. European journal of pediatrics PMID: 24737292