Background. Asthma treatment response is highly variable and pharmacogenetic markers that predict treatment response would be one step closer to personalized treatment. GWAS studies have shown that polymorphisms GLCCI1 could be associated with asthma treatment response to inhaled corticosteroids (ICS).Materials and methods. We genotyped rs37973 of GLCCI1 in 208 adult asthma patients treated with ICS. Change in % predicted FEV1 was analysed after short-term (3 months) and after long-term (at least 3 years) treatment. Treatment success was defined as good when FEV1 decreased less than 30 ml/year.Results. After 3 months of treatment, change of % predicted FEV1 was higher in patients with GG genotype than in patients with AG+AA genotype, and this genotype dependent difference was only evident in non-smokers. Similar results were found after at least 3 years of treatment when all patients were analysed, in non-smokers and patients with atopy. Even though, no differences in treatment success (good vs. poor response) were observed when analysing the entire group of patients, genotype dependent treatment success was highly influenced by smoking and atopy. GG genotype was overrepresented in non-smokers and patients with atopy with good response.Conclusions. Rs37973 was associated with short-and long-term treatment response; however, there was a great influence of smoking and atopy on pharmacogenetic association. Furthermore, we found GG genotype to be associated with better treatment response, what is contrary to results found in GWAS.Keywords: pharmacogenetics, rs37973, GLCCI1, FEV1, smoking, atopy ResumenIntroducción: La respuesta al tratamiento del asma es muy variable y los marcadores farmacogenéticos que predicen esta respuesta nos sitúan más cerca del tratamiento personalizado. Los estudios de asociación de genoma completo (GWAS) han demostrado que los polimorfismos GLCCI1 podrían estar asociados con la respuesta al tratamiento con corticosteroides inhalados (ICS).Material y métodos. Se genotipó el polimorfismo de un solo nucleótico (SNP) rs37973 de GLCCI1 en 208 pacientes adultos con asma tratados con ICS. El cambio en el porcentual de lFEV1 predicho se analizó después de un tratamiento a corto plazo (3 meses) y después de un tratamiento a largo plazo (al menos 3 años). El éxito del tratamiento se definió como bueno cuando el FEV1 disminuyó menos de 30 ml / año.Resultados. Después de 3 meses de tratamiento, el cambio en el porcentual del FEV1 predicho fue mayor en pacientes con genotipo GG que en pacientes con genotipo AG + AA, y esta diferencia asociada al genotipo solo fue evidente en los no fumadores. Se encontraron resultados similares, en el análisis de la muestra completa de pacientes, después de al menos 3 años de tratamiento, tanto en no fumadores y como en pacientes atópicos. A pesar de que no se observaron diferencias en el éxito del tratamiento (buena frente a mala respuesta) al analizar todo el grupo de pacientes, el éxito del tratamiento dependiente del genotipo estuvo muy influenciado por el...

Asthma is a chronic inflammatory disease. Around 5 to 10% of patients classified as having severe asthma can-not be adequately controlled despite the use of all currently available therapeutic approaches. Previous studies have revealed the potential important role of miRNAs in the regulation of a variety of inflammatory processes, including asthma. Expression of selected miRNAs, specifically let-7a, miR-21 and miR-223, that were shown to have important roles in asthma pathogenesis, were analyzed in bronchial biopsies of 24 patients with asthma, 12 mild and 12 severe and 10 controls with no chronic disease. We found significantly reduced expression of let-7a in bronchial biopsies from patients with severe asthma in comparison to patients with mild asthma as well as in comparison to the non-asthmatic controls. On the other hand, no significant differences in miR-21 and miR-223 expression were found between the different groups analyzed. Reduced let-7a levels in bronchial biopsies of patients with severe therapy-resistant asthma could not only be used as a potential biomarker to discriminate between different asthma phenotypes, but also might be a target for modulation of treatment at the inflammatory site for a group of patients that are most affected and still lack effective treatment.

Inhaled corticosteroids (ICS) are one of the most commonly used asthma therapies and have highly variable treatment success. Polymorphisms in TBX21, a gene important for the biological action of corticosteroids, could be associated with treatment response in asthmatics. We genotyped for rs9910408 in TBX21 in 208 adult asthmatic patients, treated at least 3 years with ICS. Polymorphism rs9910408 was associated with response to ICS treatment. When treatment success was assessed by a decrease in bronchial hyperresponsiveness (BHR), the frequency of AA genotype was significantly higher in good responders (P = 0.049). This genotype related response was even more evident in the subgroups of non-smokers (P = 0.008) and in non-atopic patients (P = 0.009). AA genotype was overrepresented among good responders according to changes in FEV1 in the subgroups of non-smokers (P = 0.013) and in non-atopic patients (P = 0.048). Our results showed that treatment response to ICS, assessed as changes in BHR and FEV1, is associated with TBX21.

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