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

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.

GLCCI1 polymorphism rs37973 and response to treatment of asthma with inhaled corticosteroids

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. Materials 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

Introducción: 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 del FEV1 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 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 tabaquismo y la atopia. El genotipo GG estaba sobrerrepresentado tanto en los pacientes no fumadores como en los pacientes con atopia, con buena respuesta al tratamiento. Conclusiones: El SNP Rs37973 se asoció con una respuesta al tratamiento con corticoides inhalados a corto y largo plazo. Sin embargo, hubo una gran influencia del tabaquismo y la atopia en esta asociación farmacogenética. Además, encontramos que el genotipo GG se asocia con una mejor respuesta al tratamiento, lo que es contrario a los resultados encontrados en otros estudios de tipo GWAS