GLCCI1 variant accelerates pulmonary function decline in patients with asthma receiving inhaled corticosteroids

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Abstract

Abstract Background In steroid‐naive patients with asthma, several gene variants are associated with a short‐term response to inhaled corticosteroid ( ICS ) treatment; this has mostly been observed in C aucasians. However, not many studies have been conducted for other ethnicities. Here, we aimed to determine the relationship between the annual decline in forced expiratory flow volume in one second ( FEV 1 ) and the variant of the glucocorticoid‐induced transcript 1 gene ( GLCCI 1 ) in Japanese patients with asthma receiving long‐term ICS treatment, taking into account the effect of high serum periostin levels, a known association factor of pulmonary function decline and a marker of refractory eosinophilic/ T h2 inflammation. Methods In this study, 224 patients with asthma receiving ICS treatment for at least 4 years were enrolled. The effects of single‐nucleotide polymorphisms ( SNP s) in GLCCI 1, stress‐induced phosphoprotein 1 ( STIP 1 ), and T gene on the decline in FEV 1 of 30 ml/year or greater were determined. Results Besides the known contributing factors, that is, the most intensive treatment step, ex‐smoking, and high serum periostin levels (≥95 ng/ml), the GG genotype of GLCC I1 rs37973, and not other SNP s, was independently associated with a decline in FEV 1 of 30 ml/year or greater. When patients were stratified according to their serum periostin levels, the GG genotype of rs37973 was significantly associated with blood eosinophilia (≥250/μl) in the high serum periostin group. Conclusions A GLCCI 1 variant is a risk factor of pulmonary function decline in J apanese patients with asthma receiving long‐term ICS treatment. Thus, GLCCI 1 may be associated with response to ICS across ethnicities.

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