GLCCI1 and STIP1 Variants are Associated with Asthma Susceptibility and Inhaled Corticosteroid Response in a Tunisian Population.

Abstract

OBJECTIVE\nPharmacogenetic 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.\n\n\nMETHODS\nWe 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.\n\n\nRESULTS\nThis 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\u2009=\u20090.001). The rs37972 and rs37973 of GLCCI1 were associated with a higher risk of asthma (p\u2009<\u20090.001). 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\u2009<\u20090.001). Also, the G allele of rs37973 was associated with worse response to ICS after 12 weeks of treatment (p <0.001).\n\n\nCONCLUSION\nThe rs37972 and rs37973 polymorphisms can serve as potential asthma risk biomarkers in a Tunisian population.