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GLCCI1 variant accelerates pulmonary function decline in patients with asthma receiving inhaled corticosteroids
Y Izuhara1, H Matsumoto, Y Kanemitsu
1Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Allergy
|March 29, 2014
Summary
A specific gene variant (GLCCI1 rs37973 GG genotype) is linked to faster lung function decline in Japanese asthma patients on inhaled corticosteroids (ICS). This finding suggests GLCCI1 may influence ICS response across diverse ethnicities.
Area of Science:
- Pulmonology
- Genetics
- Pharmacogenomics
Background:
- Inhaled corticosteroid (ICS) treatment response varies among asthma patients, with gene variants identified primarily in Caucasians.
- Limited research exists on genetic associations with ICS response in non-Caucasian populations.
- High serum periostin levels are linked to pulmonary function decline and eosinophilic inflammation in asthma.
Purpose of the Study:
- To investigate the association between the glucocorticoid-induced transcript 1 (GLCCI1) gene variant and annual decline in forced expiratory volume in one second (FEV1) in Japanese asthma patients.
- To assess the influence of high serum periostin levels on this relationship.
- To explore the role of GLCCI1 in long-term ICS treatment outcomes in an Asian population.
Main Methods:
- A cohort of 224 Japanese asthma patients on ICS for at least 4 years was studied.
- Single-nucleotide polymorphisms (SNPs) in GLCCI1, STIP1, and T genes were analyzed.
- The association between specific SNPs and an FEV1 decline of ≥30 ml/year was evaluated, considering factors like treatment intensity, smoking history, and serum periostin levels.
Main Results:
- The GG genotype of the GLCCI1 rs37973 SNP was independently associated with an FEV1 decline of ≥30 ml/year, alongside intensive treatment, ex-smoking, and high serum periostin (≥95 ng/ml).
- Other tested SNPs in GLCCI1, STIP1, and T genes did not show this independent association.
- In patients with high serum periostin levels, the GLCCI1 rs37973 GG genotype was significantly linked to blood eosinophilia (≥250/μl).
Conclusions:
- A specific variant in the GLCCI1 gene (rs37973 GG) is a risk factor for pulmonary function decline in Japanese asthma patients undergoing long-term ICS therapy.
- These findings suggest that GLCCI1 may play a role in ICS treatment response across different ethnic groups.
- The study highlights the importance of considering genetic factors and inflammatory markers like periostin for personalized asthma management.
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