Tag Archives: AHR

Blaming genes for resistance to environmental stressors

This something that I always avoided in human research – blaming genes for resistance to environmental stressors.

Nevertheless a Californian group (https://doi.org/10.1371/journal.pgen.1008528) now tested 101 mouse strains for lung resistance with exposure to diesel exhaust particles (DEP). After sensitizing the animals with dust mite and aluminium they could also test metacholine hyperreactivity (AHR).

Strains that exhibited the highest lung resistance after control exposure were not necessarily the same as those with high lung resistance after DEP exposure. It is unclear which strain was used for the consecutive GWAS. Did they put all mice into one cage for that?

The metacholine AHR GWAS results are not very impressive. And there seem to be also errors, as for example the lead SNP on chr 19 (rs51547574, near IL33) is shown with different allele frequencies in text and Fig 2.  As the expression quantitative trait locus (eQTL) for Il33 is not in the lung, I think there is nothing to memorize here – IL33 is just a gatekeeper for surface integrity.

In a next step I wouldhave expected a GWAS for resistance change after DEP but FIG 3 only gives the result of Δ AHRDEP—AHRPBS data at an abitrary methacholine dose of 10mg/ml. The identifed locus could be interesting but as the LD there is rather high without any corresponding eQTL (I always wondered why there has never been a significance threshold for LD blocks, only for isolated SNPs?), the logic of the paper is broken here. Induction of lung resistance by DEP was significantly blunted in Dapp1-/- female mice? What about male Gm5105-/- Mttp-/- , and Lamtor3-/- animals?

Hopefully nobody else will now try to find diesel, ozone, NOx resistance genes in humans as this is not a a scientific but a political issue…