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Matrix Metalloproteinase-9 (279R/Q) Polymorphism is Associated with Clinical Severity and Airflow Limitation in Tunisian Patients with Chronic Obstructive Pulmonary Disease

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Abstract

Background

The aim of this study was to investigate the role of matrix metalloproteinase-9 (MMP-9) C-1562T and 279R/Q (836G>A) polymorphisms in the development of chronic obstructive pulmonary disease (COPD) in Tunisians and to determine their impact on disease progression and airflow obstruction.

Methods

Pulmonary functional tests were evaluated by body plethysmography. MMP-9 genotypes were determined in patients with COPD (n = 138) and healthy controls (n = 216) by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). Serum MMP-9 and interleukin-6 (IL-6) levels were determined by enzyme-linked immunosorbent assays (ELISA) and activity of MMP-9 was evaluated by gelatin zymography.

Results

No significant association was found between genetic variations in MMP-9 C-1562T and 279R/Q polymorphisms and the risk of development of COPD. However, a significant correlation was retrieved between the 279 R/Q polymorphism and disease severity (P = 0.02). In addition, homozygous Q (A) genotype was associated with a poorer lung function with a fall in forced expiratory volume in 1 s (FEV1) (%) and forced vital capacity (FVC%) among COPD patients compared with both AG and GG individuals (52.06 ± 19.6 vs. 59.08 ± 17.19, P = 0.03 and 72.41 ± 21.42 vs. 82.98 ± 16.48, P = 0.002, respectively). Using ELISA, a higher level of MMP-9 was found in patients with the CT genotype (P = 0.03), while no significant impact of the 279R/Q polymorphism was observed (P = 0.48). In contrast, by using zymography gel analysis, MMP-9 activity was enhanced in individuals carrying the R(G) allele in comparison with those homozygous for the Q(A) variant (P = 0.02).

Conclusion

Our results support a role for the 279R/Q polymorphism in physiological alterations that may affect progression and severity of COPD. These findings could be related to the decreased activity of MMP-9 among COPD patients carrying the 279Q variant.

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Acknowledgments

This work was supported by the Ministry of Higher Education and Scientific Research and by the Ministry of Public Health of the Tunisian Government. The authors wish to thank all of the patients and controls who participated in this study.

Author information

Authors and Affiliations

  1. Unité de recherche UR12ES06, Physiologie de l’Exercice et Physiopathologie: de l’Intégré au Moléculaire “Biologie, Médecine et Santé”, Faculté de Médecine de Sousse, Université de Sousse, Sousse, Tunisia

    Sarra Bchir, Hela ben Nasr, Amel ben Anes, Zouhair Tabka & Karim Chahed

  2. Institut Supérieur de Biotechnologie de Monastir, Université de Monastir, Monastir, Tunisia

    Sarra Bchir

  3. Institut des Sciences Infirmières, Sousse, Tunisia

    Hela ben Nasr

  4. Laboratoire de Biotechnologie, Faculté des Sciences de Sfax, Sfax, Tunisia

    Imen Rekik Hakim

  5. Faculté des Sciences de Bizerte, Université de Carthage, Tunis, Tunisia

    Amel ben Anes

  6. Unité de Recherche “UR06SP05” Centre Régional de Transfusion Sanguine, CHU Farhat Hached, Sousse, Tunisia

    Saloua Yacoub

  7. Service de Pneumo-Allergologie, CHU Farhat Hached, Sousse, Tunisia

    Abdelhamid Garrouch & Mohamed Benzarti

  8. INSERM U1138, Université Pierre et Marie Curie, Université Paris-Descartes, Centre de Recherche des Cordeliers, Paris, France

    Brigitte Bauvois

  9. Faculté des Sciences de Sfax, Université de Sfax, Sfax, Tunisia

    Karim Chahed

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  1. Sarra Bchir
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Correspondence to Karim Chahed.

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Conflict of interest

The authors SB, HbN, IRH, AbA, SY, AG, MB, BB, ZT, and KC have no conflicts of interest that are directly relevant to the content of this article.

Funding

The authors SB, HbN, IRH, AbA, SY, AG, MB, BB, ZT, and KC declare that this study was funded by the Tunisian Ministry of Higher Education and Research (UR12ES06).

Ethical approval and informed consent

The study was approved by the local ethical committee of Farhat Hachad Hospital (Sousse, Tunisia; approval number: 08-2011).

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Bchir, S., Nasr, H.b., Hakim, I.R. et al. Matrix Metalloproteinase-9 (279R/Q) Polymorphism is Associated with Clinical Severity and Airflow Limitation in Tunisian Patients with Chronic Obstructive Pulmonary Disease. Mol Diagn Ther 19, 375–387 (2015). https://doi.org/10.1007/s40291-015-0163-2

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