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.
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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.
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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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DOI: https://doi.org/10.1007/s40291-015-0163-2