GLCCI1 and STIP1 variants are associated with asthma susceptibility and inhaled corticosteroid response in a Tunisian population

Abstract

Objective: Pharmacogenetic studies have recognized specific genes that highly correlate with response to inhaled corticosteroids (ICS) treatment in asthma patients. Among the genes identified, we selected glucocorticoid-induced transcript 1 (GLCCI1) and stress-induced phosphoprotein 1 (STIP1) to evaluate the impact of these gene polymorphisms on ICS treatment response in Tunisian asthmatics.

Methods: We analyzed four single nucleotide polymorphisms (SNPs): two in GLCCI1 (rs37972 and rs37973), and two in STIP1 (rs2236647 and rs2236648), which are genes associated with susceptibility to asthma and response to ICS in a Tunisian cohort. The SNPs were genotyped using reverse transcriptase polymerase chain reaction (RT-PCR) techniques.

Results: This case–control study consisted of 230 adult asthmatic patients and 236 healthy subjects. Seventy-five asthmatics were selected and followed through 12 weeks of routine treatment. The T allele rs2236648 in STIP1 was associated with allergic asthma (OR = 0.38, 95%CI = 0.20–0.69, p = 0.001). The rs37972 and rs37973 of GLCCI1 were associated with a higher risk of asthma (p < 0.001). The T allele rs37972 and G allele rs37973 were correlated with a strong risk for developing severe asthma (p < 0.001). Asthma patients carrying the rs37973 GG genotype had less improvement in the forced expiratory volume in one second (FEV1) than those with the AA or AG genotypes after 12 weeks of treatment (p < 0.001). Also, the G allele of rs37973 was associated with worse response to ICS after 12 weeks of treatment (p < 0.001).

Conclusion: The rs37972 and rs37973 polymorphisms can serve as potential asthma risk biomarkers in a Tunisian population.

Keywords:

• Asthma risk
• glucocorticoid
• lung function
• SNPs association

Acknowledgments

We especially need to thank Professor Jia Haibo (Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Human Genome Research Center) Huazhong University of Science and Technology; Wuhan, China. We are grateful to all contributors who provided data to our team.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.

Additional information

Funding

This study was supported by the grant from ‘‘the Ministry of research of Tunisia: El Manar Tunis University.