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


Salhi M(1)(2)(3), Lahmar O(1)(2)(3), Salah MO(1)(2)(3), Banić I(4), Binghao B(5), Malik W(6), Hamzaoui K(2)(3)(7), Turkalj M(8)(9), Hamzaoui A(2)(3)(6).
Author information:
(1)Faculty of Sciences, University of Tunis el Manar, Tunis, Tunisia.
(2)Unit Research 12SP15 "Homeostasis and Molecular Dysfunction in the lung" Abderrahman Mami Hospital, Pavillon B, Ariana, Tunisia.
(3)Medical Faculty of Tunis, University of Tunis el Manar, Rabta, Tunis, Tunisia.
(4)Department of Translational Medicine, Srebrnjak Children's Hospital, Zagreb, Croatia.
(5)College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China.
(6)Department of Respiratory and Critical Care Medicine, National Clinical Research Center of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
(7)Division of Pediatric Respiratory Diseases, Pavilion B, A. Mami Hospital, Ariana, Tunisia.
(8)Department of Pulmonology and Allergology, Srebrnjak Children's Hospital, Zagreb, Croatia.
(9)Faculty of Medicine, J.J. Strossmayer University of Osijek, Osijek, Croatia.


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.