Genetic evaluation of the effect of GLCCI1 rs37973 on corticosteroid response in chronic obstructive pulmonary disease

Abstract

The efficacy of inhaled corticosteroids (ICS) for chronic obstructive pulmonary disease (COPD) varies between patients, which may be partially due to genetic differences. A single-nucleotide polymorphism, rs37972, in the glucocorticoid-induced transcript 1 gene (GLCCI1) has been associated with variations in response (forced expiratory volume in 1 s [FEV1] and residual volume) to fluticasone propionate (Groningen and Leiden Universities Study of Corticosteroids in Obstructive Lung Disease [GLUCOLD] study). The aim of this study was to determine whether variation in the GLCCI1 gene at rs37973 is associated with ICS response in patients with COPD. Variations in the GLCCI1 gene, rs37973 (which is in almost complete linkage disequilibrium with rs37972) were examined in 402 corticosteroid-treated, non-Hispanic Caucasian COPD patients, and in 63 GLUCOLD study patients. We were unable to confirm a genetic association between GLCCI1 and change in FEV1, unlike equivalent data generated for rs37973 from the GLUCOLD study sample. This was despite accounting for differences in gender, baseline FEV1, severity of COPD, extent of reversibility, and combination therapy of ICS with bronchodilators. We conclude that based on changes in FEV1, there is no evidence that the GLCCI1 variant rs37973 has an impact on corticosteroid response in patients with COPD. GSK study number HZC112206 (ClinicalTrials.gov identifier: NCT01053988 . Registered January 14 2010) and HZC112207 (ClinicalTrials.gov identifier: NCT01054885 . Registered January 14 2010).