Gene environment interactions in asthma

Article Outline

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The availability of the human genome sequence has changed the way we think of disease risk and pathogenesis. Shortly after high density sequencer information became available, it became clear that there is remarkable sequence variation among humans. These sequence variations (single nucleotide polymorphisms or SNPs) account, in part, for not only our individual variation but our susceptibility to disease and individual responses to medications. Witness the birth of the field of pharmacogenomics. These variations can explain other patterns of disease risk where the precise phenotype-genotype correlations are unclear and variations in susceptibility to exposures. Thus, besides genetic variations, there is growing recognition that gene environment interactions account for some of the heterogeneity in disease risk. In this issue of The Journal, Schroer et al report just such an association between diesel exhaust particles, environmental tobacco smoke, and mold with a polymorphism in the glutathione S-transferase gene. Their results demonstrate an increased risk of symptomatic wheezing in infants with one genotype and, remarkably, some modest protection by another genotype that could be overwhelmed by multiple environmental exposures. This effect was most significant among non-Caucasian study subjects. A report that raises as many questions as it answers is intriguing, and this work suggests many different important considerations for future directions of research in both the etiology and treatment of childhood asthma. The overlay of contemporary insights provided by the genetic analyses makes for worthwhile reading and consideration of other settings for future investigation.