GLCCI1 rs37973 and inhaled corticosteroids: findings from a European cohort of COPD patients

Glucocorticoid-induced transcript 1 (<italic>GLCCI1</italic>) is related to the occurrence of asthma, as well to responsiveness to inhaled corticosteroids (ICS) in patients mainly of Asian origin. Our objective was to investigate the association between rs37973 and response to ICS in a European cohort of COPD patients. 165 COPD patients from the HISTORIC study, an investigator-initiated and -driven randomized, double-blind, placebo-controlled trial, were genotyped for the functional SNV rs37973 in the <italic>GLCCI1</italic> gene. Patients’ response to ICS was assessed based on FEV₁ change and health-related QoL questionnaires. At baseline, GG carriers presented with significantly lower values in single breath N2 washout % predicted (p=0.004) while they exhibited higher post-bronchodilator FEV₁ % predicted (p=0.003), compared to A carriers. After 6-week treatment of ICS, AA carriers, naïve to ICS, improved significantly in terms of FEV₁ compared to G carriers (p=0.008). GG carriers who took ICS showed a significant improvement in FEV₁ over the following 12-month intervention, with an average gain of 80 ml, whereas GG carriers in the placebo group experienced an average loss of 20 ml. Consistent with FEV₁ data changes in SGQR and CAT scores over 12 months were observed. GG carriers who underwent ICS treatment exhibited an average decrease of 8 units in SGQR and an improvement of 10 points in CAT score, both of which are clinically significant, compared to A carriers that had no significant changes. These results imply intriguing links between rs37973 genotypes and the response to ICS treatment in COPD patients, a relationship seemingly influenced by the duration of therapy, whether short-term or long-term.