M Rijavec1, M Žavbi1, A Lopert2, M Fležar1, P Korošec1. 1. University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia. 2. Outpatient Practice for Pulmonary Diseases and Allergy, Murska Sobota, Slovenia.
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.
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 asthmapatients. MATERIAL AND METHODS: We genotyped rs37973 in GLCCI1 in 208 adult asthmapatients 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.
Authors: Jesús Miguel García-Menaya; Concepción Cordobés-Durán; Elena García-Martín; José A G Agúndez Journal: Front Pharmacol Date: 2019-05-21 Impact factor: 5.810