Sandra Dragicevic1, Mitja Kosnik2, Aleksandra Divac Rankov3, Matija Rijavec2, Katarina Milosevic4, Peter Korosec2, Maja Skerbinjek Kavalar5,6, Aleksandra Nikolic3. 1. Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 11010, Belgrade, Serbia. sandra.d@imgge.bg.ac.rs. 2. University Clinic of Respiratory and Allergic Diseases Golnik, Golnik 36, 4204, Golnik, Slovenia. 3. Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 11010, Belgrade, Serbia. 4. Department of Pulmonology and Allergology, University Children's Hospital, Tirsova 10, 11000, Belgrade, Serbia. 5. University Clinical Centre Maribor, Ljubljanska Ulica 5, 2000, Maribor, Slovenia. 6. Private Practice Cebelica, Lavričeva Ulica 1a, 2000, Maribor, Slovenia.
Abstract
PURPOSE: The maintaining of asthma control is difficult due to high variability in response to therapy among patients. Since matrix metalloproteinase 9 (MMP9) is implicated in inflammation and remodeling of asthmatic airways, it could be associated with adequate response to asthma therapy. The aim of this study was to investigate whether variants in 3' end of the MMP9 gene are associated with clinical phenotype and responsiveness to treatment in children with asthma. METHODS: The study included 127 asthmatic children from Slovenia. Variants in the 3' end of the MMP9 gene were analyzed by direct DNA sequencing and the obtained results were correlated with clinical parameters. RESULTS: Two variants were detected, rs13925 and rs20544. For the variant rs20544, statistically significant difference in airway hyperresponsiveness (p = 0.011) and asthma control (p = 0.049) between genotypes was found. Patients with TT genotype had lower airway sensitivity, and after 12 months of treatment showed significant improvement in Asthma Control Test (ACT) scores compared to CC and CT genotype. For the variant rs13925, the association with lung function was observed. The carriers of A allele showed noticeable improvement of lung function after the first 6 months of treatment in comparison to the carriers of G allele (p = 0.046). CONCLUSION: The main finding of our study is the association of MMP9 genotypes rs20544 TT and rs13925 AA and AG with better asthma control, and indirectly better response to treatment. Based on these results, MMP9 deserves further research as a potential predictive biomarker for asthma.
PURPOSE: The maintaining of asthma control is difficult due to high variability in response to therapy among patients. Since matrix metalloproteinase 9 (MMP9) is implicated in inflammation and remodeling of asthmatic airways, it could be associated with adequate response to asthma therapy. The aim of this study was to investigate whether variants in 3' end of the MMP9 gene are associated with clinical phenotype and responsiveness to treatment in children with asthma. METHODS: The study included 127 asthmatic children from Slovenia. Variants in the 3' end of the MMP9 gene were analyzed by direct DNA sequencing and the obtained results were correlated with clinical parameters. RESULTS: Two variants were detected, rs13925 and rs20544. For the variant rs20544, statistically significant difference in airway hyperresponsiveness (p = 0.011) and asthma control (p = 0.049) between genotypes was found. Patients with TT genotype had lower airway sensitivity, and after 12 months of treatment showed significant improvement in Asthma Control Test (ACT) scores compared to CC and CT genotype. For the variant rs13925, the association with lung function was observed. The carriers of A allele showed noticeable improvement of lung function after the first 6 months of treatment in comparison to the carriers of G allele (p = 0.046). CONCLUSION: The main finding of our study is the association of MMP9 genotypes rs20544 TT and rs13925 AA and AG with better asthma control, and indirectly better response to treatment. Based on these results, MMP9 deserves further research as a potential predictive biomarker for asthma.
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