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GLCCI1 多态性 rs37973 与吸入皮质类固醇治疗哮喘的反应。

GLCCI1 Polymorphism rs37973 and Response to Treatment of Asthma With Inhaled Corticosteroids.

机构信息

University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia.

Outpatient Practice for Pulmonary Diseases and Allergy, Murska Sobota, Slovenia.

出版信息

J Investig Allergol Clin Immunol. 2018;28(3):165-171. doi: 10.18176/jiaci.0229. Epub 2018 Jan 17.

Abstract

BACKGROUND

The response to asthma treatment is highly variable, and having pharmacogenetic markers that predict response to treatment would bring us one step closer to personalized treatment. Genome-wide association studies have shown that polymorphisms in GLCCI1 could be associated with the response to inhaled corticosteroids (ICSs) in asthma patients.

MATERIAL AND METHODS

We genotyped rs37973 in GLCCI1 in 208 adult asthma patients treated with ICSs. The percentage change in FEV1, % predicted was analyzed after short-term treatment (3 months) and long-term treatment (at least 3 years). Treatment was defined as successful when FEV1 decreased by <30 mL/year.

RESULTS

After 3 months of treatment, FEV1, % predicted was higher in patients with the GG genotype than in patients with the AG+AA genotype, and this genotype-dependent difference was only evident in nonsmokers. Similar results were found in nonsmokers and patients with atopy after at least 3 years of treatment, when all patients were analyzed. Even though no differences were observed for success of treatment (good vs poor response) when the whole group of patients was analyzed, genotype-dependent treatment success was highly influenced by smoking and atopy. The GG genotype was overrepresented in nonsmokers and patients with atopy and a good response.

CONCLUSIONS

rs37973 was associated with response to short- and long-term treatment; however, smoking and atopy had a considerable effect on pharmacogenetic association. Furthermore, in contrast with findings from genome-wide association studies, we found the GG genotype to be associated with better treatment response.

摘要

背景

哮喘治疗的反应差异很大,拥有预测治疗反应的遗传标记将使我们更接近个体化治疗。全基因组关联研究表明,GLCCI1 中的多态性可能与哮喘患者吸入皮质类固醇(ICSs)的反应有关。

材料和方法

我们在 208 名接受 ICSs 治疗的成年哮喘患者中对 GLCCI1 中的 rs37973 进行了基因分型。在短期治疗(3 个月)和长期治疗(至少 3 年)后,分析了 FEV1(预计百分比的变化)。当 FEV1 每年下降<30 毫升时,将治疗定义为成功。

结果

在治疗 3 个月后,GG 基因型患者的 FEV1,预计百分比高于 AG+AA 基因型患者,这种基因型依赖性差异仅在非吸烟者中明显。在至少 3 年的治疗后,当所有患者均进行分析时,非吸烟者和特应性患者中也发现了类似的结果。即使当分析整个患者组时,治疗成功(良好反应与不良反应)没有差异,但基因型依赖性治疗成功受到吸烟和特应性的显著影响。在非吸烟者和特应性患者以及良好反应者中,GG 基因型的比例过高。

结论

rs37973 与短期和长期治疗反应相关;然而,吸烟和特应性对药物遗传学关联有很大影响。此外,与全基因组关联研究的结果相反,我们发现 GG 基因型与更好的治疗反应相关。

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