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

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 p p p Conclusion: The rs37972 and rs37973 polymorphisms can serve as potential asthma risk biomarkers in a Tunisian population.研究目标：药物基因组学（Pharmacogenetics）研究已证实，部分基因与哮喘患者吸入性糖皮质激素（inhaled corticosteroids, ICS）治疗应答高度相关。本研究从已鉴定的基因中选取糖皮质激素诱导转录本1（glucocorticoid-induced transcript 1, GLCCI1）与应激诱导磷酸蛋白1（stress-induced phosphoprotein 1, STIP1），旨在评估这两个基因的多态性对突尼斯哮喘患者ICS治疗应答的影响。 研究方法：本研究分析了4个单核苷酸多态性（single nucleotide polymorphisms, SNPs）位点：GLCCI1基因上的2个位点（rs37972与rs37973），以及STIP1基因上的2个位点（rs2236647与rs2236648），上述基因均与突尼斯队列人群的哮喘易感性及ICS治疗应答相关。采用逆转录聚合酶链反应（reverse transcriptase polymerase chain reaction, RT-PCR）技术对上述SNPs位点进行基因分型。 研究结果：本病例对照研究共纳入230名成人哮喘患者与236名健康受试者。其中75名哮喘患者被选取并接受为期12周的常规治疗随访。STIP1基因rs2236648位点的T等位基因与过敏性哮喘显著相关（比值比OR=0.38，95%置信区间CI=0.20–0.69，p=0.001）。GLCCI1基因的rs37972与rs37973位点多态性与哮喘更高发病风险相关（p p p p）。 研究结论：rs37972与rs37973位点多态性可作为突尼斯人群潜在的哮喘风险生物标志物。