Wednesday, 19 October 2011

Glad I MET you

Another choice paper has emerged from the MIND Institute on everyone's favourite topic, autoimmunity and autism. The full-text paper by Heuer and colleagues* (including Judy Van de Water and Paul Ashwood on the authorship list) looked at the the MET gene in mums of children with autism vs. controls and how variations to it may relate to the the presence of autoantibodies to foetal brain and the production of messenger cytokines.

For those of you who might not have met MET before (!) this is a gene which has attracted quite a bit of interest with regards to autism spectrum conditions down the years. The International Molecular Genetic Study of Autism Consortium (IMGSAC), which I am not entirely sure is still functioning following the move of one of the heads quite recently, published quite a bit on this gene and its possible connection to autism. This and other findings have been quite robust in their results. Even other compounds tied into the MET gene functions, such as hepatocyte growth factor seems to tie into some of the genetic findings of the gene. One of the most comprehensive overviews of MET that I have read is on this blog.

Dare I also mention a possible link between MET and gastrointestinal factors associated with some cases of autism?

Anyhow, the current paper discusses some further interesting developments on a possible MET-autism relationship. The basics and summary:

  • Mums of children with an autism spectrum condition (n=202) were compared with mums of control children (n=163) as part of the CHARGE study. This means that the authors were about as positive as they were ever going to be that what they saw in their autism group was autism and the control group was not-autism.
  • Mums' samples were assayed for a band pattern of maternal antibodies to foetal brain proteins (37 + 73-kDa) and genotyped for the MET gene, specifically the SNP associated with autism (rs1858830) and various cytokines and chemokines. 
  • The results: 19 mums of children with autism (9%) showed antibody patterns to foetal brain compared with zero controls. Among this subgroup of 19, 11 were homozygous for the C allele SNP (remember back to my post where I mentioned zygosity... if you dare); 7 of the remaining were heterozygous for the SNP and 1 didn't show the variant. 
  • Even among those mums of children with autism who were negative for the foetal brain band stuff, 28% were homozygous for the SNP, 43% heterozygous and roughly a quarter did not show the variant at all (29%).
  • The authors conclude that the MET C allele frequency was higher in those mums of children with autism who presented with antibodies compared with those who did not show antibodies to foetal brain protein despite there being some overlap.
  • Furthermore, those with the SNP (whether homozygous or heterozygous) showed significantly reduced MET protein levels compared with non-variant homozygous controls; albeit with variant (C allele) homozygous participants showing only slightly lower levels of the protein than heterozygous participants (whose mean amount figures don't appear to be given in the paper). 
  • When comparing geneotype data and cytokine data, those with the SNP showed some significant correlation between their SNP, levels of the MET protein and the production of IL-10 (an anti-inflammatory cytokine). If mums were homozygous for the SNP variant, there was a 1.8 fold decrease in IL-10 although no specific data seems to be provided for the variant heterozygous group aside from a graph showing an almost comparable drop in IL-10 production. There were no other significant differences/associations with the other six cytokines/chemokines included for analysis.

I probably have not done the results justice with this brief summary but I hope you get the gist of what they found. It is a rather 'dense' set of results they produced and I have to admit, my head is hurting a little after going through them all so please do not take my word as Gospel.

The MIND Institute have been pretty much leaders on the analysis of gene-environment interactions in autism in recent times with a particular focus on the immune system. This is not another of their studies fitting into this category as opposed to the SNPs and vits study published earlier this year, given the current study focusing on genes controlling biochemistry. Having said that no-one, as yet, seems to be able to say where and how these SNPs might originate; whether it is just a chance, random phenomenon or something tied into environment, perhaps even when mums (and dads) were conceived? Should we be looking at grandparents also?

I note that the words 'genetic test' for autism risk have already surfaced on the back of these results. I am staying well away from this area for lots of reasons; not least because the results are not black-and-white and that this is more of an ethical area of discussion.

* Heuer L. et al. Association of a MET genetic variant with autism-associated  maternal autoantibodies to fetal brain proteins and cytokine expression. Translational Psychiatry. October 2011.