Recent genomic studies have begun to demonstrate that adaptive genotypes are only adaptive when expressed in their relevant context. In this month’s issue, Ege et al. and the European consortium, GABRIEL, present surprising findings from a gene-environment (G*E) interaction analysis for childhood asthma and the farming environment (J Allergy Clin Immunol 2011;127:138-144.e4).
Ege et al. report that previously identified common SNPs associated with asthma in urban populations did not interact with farming environment parameters. Previously identified interactions with farming related exposures were not confirmed despite adequate statistical power.
Among rarer SNPs, however, significant interactions were detected with farming related exposures such as
consumption of raw milk, and exposure to cow and/or straw. By this approach the authors identified new genes that differed from those reported as asthma-associated. SNPs in the GRM1 (metabotropic glutamate receptor 1) gene specifically and significantly interacted with farm exposures. The GRM1 is involved in immunological and neuronal synaptic function. The authors note that these results must be interpreted carefully as the SNPs are rare.
Ege et al. conclude that there may exist different phenotypes of asthma that are susceptible to either genetic or environmental effects, but rarely to both at the same time. They propose that genotypes which are protective for one exposed population do not carry an effect in an unexposed population.
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