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The Variants in the 3′ Untranslated Region of the Matrix Metalloproteinase 9 Gene as Modulators of Treatment Outcome in Children with Asthma

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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.

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Funding

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.

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Authors and Affiliations

  1. Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 11010, Belgrade, Serbia

    Sandra Dragicevic, Aleksandra Divac Rankov & Aleksandra Nikolic

  2. University Clinic of Respiratory and Allergic Diseases Golnik, Golnik 36, 4204, Golnik, Slovenia

    Mitja Kosnik, Matija Rijavec & Peter Korosec

  3. Department of Pulmonology and Allergology, University Children’s Hospital, Tirsova 10, 11000, Belgrade, Serbia

    Katarina Milosevic

  4. University Clinical Centre Maribor, Ljubljanska Ulica 5, 2000, Maribor, Slovenia

    Maja Skerbinjek Kavalar

  5. Private Practice Cebelica, Lavričeva Ulica 1a, 2000, Maribor, Slovenia

    Maja Skerbinjek Kavalar

Authors
  1. Sandra Dragicevic
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  2. Mitja Kosnik
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  3. Aleksandra Divac Rankov
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  4. Matija Rijavec
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  5. Katarina Milosevic
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  7. Maja Skerbinjek Kavalar
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  8. Aleksandra Nikolic
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Correspondence to Sandra Dragicevic.

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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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Dragicevic, S., Kosnik, M., Divac Rankov, A. et al. The Variants in the 3′ Untranslated Region of the Matrix Metalloproteinase 9 Gene as Modulators of Treatment Outcome in Children with Asthma. Lung 196, 297–303 (2018). https://doi.org/10.1007/s00408-018-0113-y

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  • DOI: https://doi.org/10.1007/s00408-018-0113-y

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