@article {Tantisira1871, author = {Kelan Tantisira and Jessica Lasky-Su and Michishige Harada and Amy Murphy and Augusto Litonjua and Blanca Himes and Christoph Lange and Ross Lazarus and Jody Sylvia and Barbara Klanderman and Qingling Duan and Weiliang Qiu and Tomomitsu Hirota and Fernando Martinez and Dave Mauger and Christine Sorkness and Stanley Szefler and Stephen Lazarus and Robert Lemanske and Stephen Peters and John Lima and Yusuke Nakamura and Mayumi Tamari and Scott Weiss}, title = {Late-breaking abstract: Genome-wide association of GLCCI1 with asthma steroid treatment response}, volume = {38}, number = {Suppl 55}, elocation-id = {1871}, year = {2011}, publisher = {European Respiratory Society}, abstract = {Background: Asthma treatment response is characterized by wide inter-individual variability and a significant number of non-responders.Aims: We hypothesized that a genome-wide association study would yield novel determinants of inhaled glucocorticosteroid (ICS) response in asthma.Methods: We analyzed change in FEV1 following ICS usage in a small number of statistically powerful variants selected via a family-based screening algorithm on 534,290 single nucleotide polymorphisms genotyped in the Childhood Asthma Management Program. Finding a significant, replicated association, we characterized its functional effects.Results: We identified a significant pharmacogenetic association at rs37972, which was replicated in four independent populations totaling 935 individuals (p=0.0007). This variant maps to the glucocorticoid induced transcript 1 (GLCCI1) gene and is in complete linkage disequilibrium (i.e., perfectly correlated) with rs37973; both are associated with decrements in GLCCI1 expression. In isolated cell systems the rs37973 variant is associated with significantly decreased luciferase reporter activity; in pooled data from treatment trials patients with the variant allele have reduced FEV1 responses to ICS (pooled p=0.0007). Overall, subjects homozygous for the mutant rs37973 allele had only 1/3 the FEV1 increase on inhaled corticosteroids vs. those homozygous wild type (3.2{\textpm}1.6\% vs. 9.4{\textpm}1.1\%), accompanied by a significantly higher risk of a poor (i.e. lowest quartile) response (OR 2.36, 95\% CI: 1.24-4.51), with genotype accounting for \~{}6.6\% of response variability.Conclusion: A functional GLCCI1 variant is associated with substantial decrements in inhaled glucocorticosteroid response in asthma.}, issn = {0903-1936}, URL = {https://erj.ersjournals.com/content/38/Suppl_55/1871}, eprint = {https://erj.ersjournals.com/content}, journal = {European Respiratory Journal} }