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GLCCI1 polymorphism rs37973 and asthma treatment response to inhaled corticosteroids

Rijavec M1, Žavbi M1, Lopert A2, Fležar M, Korošec P1

1University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia
2Outpatient practice for pulmonary diseases and allergy, Murska Sobota, Slovenia

J Investig Allergol Clin Immunol 2018; Vol. 28(3)
doi: 10.18176/jiaci.0229

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.

Key words: Pharmacogenetics, rs37973, GLCCI1, FEV1, Smoking, Atopy