About a third of individuals with asthma who use inhaled glucocorticoids do not respond to this form of anti-inflammatory asthma control. Heterogeneity in the levels of endogenous glucocorticoids partially explains the observed variation, but family studies also suggest heritable components in the differential response to glucocorticoids. A new study reports that the promoter region of GLCCI1 harbors two linked SNP markers associated with glucocorticoid response (N. Engl. J. Med. 365, 1173–1183, 2011). The discovery was made using a family-based genome-wide screen in 403 child-parent trios, including 118 affected children who received budesonide, and was subsequently validated in four trial data sets. Individuals homozygous for the risk alleles have a 2.36-fold greater chance of poor response to inhaled glucocorticoids, and their mean improvement in a standard lung function measurement is only 30% of that of people with wild-type alleles. Reporter assays showed that the risk haplotype reduces GLCCI1 transcription; however, the transcription factors involved and the function of the GLCCI1 protein remain unknown. Together with a recent report of a phase 2 trial for lebrikizumab, in which serum periostin level accurately predicted efficacy (N. Engl. J. Med. 365, 1088–1098, 2011), this study brings us closer to personalized asthma treatment.
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Peng, W. Personalized asthma control. Nat Genet 43, 1178 (2011). https://doi.org/10.1038/ng.1023
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DOI: https://doi.org/10.1038/ng.1023