Wednesday, 11 December 2013

Even more air pollution and autism risk findings

Air pollution.

I'm pretty sure most people are aware of all the talk about air pollution these days and how the human body is not particularly fond of air pollution in terms of potential adverse health outcomes (assuming that is, you leave things like selenium out of the equation). If you happen to live in China, I'm sure your mind was put at ease when reading about 'The Five Surprising Gains from the Smog'... or maybe not.

Most people generally find it easier to accept that air pollution might show a possible connection with something like respiratory diseases for example, given that the airways are generally a first point of entry for said pollution getting access to the body (although not the only route). Mention that something like autism risk for example, might also be linked to air pollution exposure and I'm sure that a significant degree of eye-rolling begins, alongside mutterings of the old 'correlation is not the same as causation' argument.
The Alchemist @ Wikipedia 

Personally I'm quite intrigued by the results emerging looking at something like childhood or maternal exposure to air pollution and proximity to sources of air pollution being linked to child or offspring autism risk. In these times of the autisms and various external forces implicated in autism risk (think valproate for example and the recent special reminder from the MHRA on this matter; even someone mentioning the word 'proven' [1] as if such a thing exists) I don't think we can rule most things out yet.

You have for example, the data from Heather Volk and colleagues [2] which was talked about in this post compounded by the data from Tracy Ann Becerra and colleagues [3] (see this post) both quite recently pinpointing something of a statistical association at least. That and other studies looking at a possible association.

Enter then another study by Volk and colleagues [4] which adds another layer of intrigue and complexity to the air pollution link by suggesting that a certain kind of genotype combined with air pollution exposure might elevate the risk of autism. There has been some media coverage of this paper (see here).

I suppose the first thing to take from the latest Volk paper is it's concentration on gene x environment interactions potentially modifying the risk of something like autism. I'm sure readers are used to hearing about [variable] gene-environment interactions quite loudly proclaimed these days as accounting for the presence of autism, but to see a study looking experimentally at the issue is very refreshing.

The next thing to note about the Volk paper is the specific focus on the MET receptor tyrosine kinase (MET) gene and a particular version of this gene potentially interacting with something like air pollution. In the post titled: 'I'm glad I MET you' (no prizes for the headline there) I talked about some other rather interesting findings when it came to MET and autism. Alongside all the chatter about things like synaptic development which MET has been tied to [5] was the suggestion that "the functional MET promoter variant rs1858830 C allele was strongly associated with the presence of an ASD-specific 37+73-kDa band pattern of maternal autoantibodies to fetal brain proteins (P=0.003)" as per the paper from Heuer and colleagues [6]. Maternal autoantibodies, as regular readers might know, are an upcoming area with autism risk in mind (see here).

It is then perhaps no surprise that the MET rs1858830 genotype, same as that one looked at with maternal autoantibodies in mind, was also the focus on the recent Volk paper and in particular the 'CC' genotype (see here for some information on zygosity). This genotype seems to be one which is more commonly noted in relation to cases of autism [7]. Indeed, based on an analysis of participants involved with the CHARGE initiative (beincharge!) the authors suggested: "Subjects with both MET rs1858830 CC genotype and high air pollutant exposures were at increased risk of autism spectrum disorder compared with subjects who had both the CG/GG genotypes and lower air pollutant exposures". Big words, I'm sure you'll agree.

These results are obviously crying out for replication for starters. The focus of this study was (a) on one gene, one specific variant of one gene, in our entire genome (b) looking at structural issues with said gene not necessarily gene function as per that rising star which is epigenetics for example might have on gene expression, and (c) based on air pollution exposure estimates from "local traffic-related sources and regional sources (particulate matter, nitrogen dioxide, and ozone)". With those factors in mind, caution still needs to be applied to these results before anyone goes and tries to for example, market any sort of genetic test for air pollution related autism or anything similar... Oh and 'steering clear of cities' is probably not a realistic option for most people either. Indeed, even residing in the countryside has been linked to autism risk (see here).

But still I'm interested in these results and indeed, the next question of biological processes from genes to environment to development and behaviour.

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[1] Harden CL. In Utero Valproate Exposure and Autism: Long Suspected, Finally Proven. Epilepsy Currents 2013; November/December 2013: 13; 282-284.

[2] Volk HE. et al. Traffic-related air pollution, particulate matter, and autism. JAMA Psychiatry. 2013 Jan;70(1):71-7.

[3] Becerra TA. et al. Ambient air pollution and autism in Los Angeles county, California. Environ Health Perspect. 2013 Mar;121(3):380-6.

[4] Volk HE. et al. Autism Spectrum Disorder: Interaction of Air Pollution with the MET Receptor Tyrosine Kinase Gene. Epidemiology. 2013 Nov 14.

[5] Judson MC. et al. A new synaptic player leading to autism risk: Met receptor tyrosine kinase. J Neurodev Disord. 2011 Sep;3(3):282-92.

[6] Heuer L. et al. Association of a MET genetic variant with autism-associated maternal autoantibodies to fetal brain proteins and cytokine expression. Transl Psychiatry. 2011 Oct 18;1:e48. doi: 10.1038/tp.2011.48.

[7] Jackson PB. et al. Further evidence that the rs1858830 C variant in the promoter region of the MET gene is associated with autistic disorder. Autism Res. 2009 Aug;2(4):232-6. doi: 10.1002/aur.87.

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ResearchBlogging.org Volk HE, Kerin T, Lurmann F, Hertz-Picciotto I, McConnell R, & Campbell DB (2013). Autism Spectrum Disorder: Interaction of Air Pollution with the MET Receptor Tyrosine Kinase Gene. Epidemiology (Cambridge, Mass.) PMID: 24240654