The Variants in the 3′ Untranslated Region of the Matrix Metalloproteinase 9 Gene as Modulators of Treatment Outcome in Children with Asthma
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.
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.
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).
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.
Keywords3′ UTR Genotype Matrix metalloproteinase Variant
The research was supported by the Grant P3-0360 from the Slovenian Research Agency and by the Grant 173008 of the Ministry of Education, Science and Technological Development of the Republic of Serbia.
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical Approval and Informed Consent
The study was in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Written informed consent was obtained for all patients and the investigation was approved by the hospital ethical committee.
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