Sarra Bchir1,2, Hela Ben Nasr1,3, Imen Rekik Hakim4, Amel Ben Anes1,5, Saloua Yacoub6, Abdelhamid Garrouch7, Mohamed Benzarti7, Brigitte Bauvois8, Zouhair Tabka1, Karim Chahed9,10. 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. 2. Institut Supérieur de Biotechnologie de Monastir, Université de Monastir, Monastir, Tunisia. 3. Institut des Sciences Infirmières, Sousse, Tunisia. 4. Laboratoire de Biotechnologie, Faculté des Sciences de Sfax, Sfax, Tunisia. 5. Faculté des Sciences de Bizerte, Université de Carthage, Tunis, Tunisia. 6. Unité de Recherche "UR06SP05" Centre Régional de Transfusion Sanguine, CHU Farhat Hached, Sousse, Tunisia. 7. Service de Pneumo-Allergologie, CHU Farhat Hached, Sousse, Tunisia. 8. INSERM U1138, Université Pierre et Marie Curie, Université Paris-Descartes, Centre de Recherche des Cordeliers, Paris, France. 9. 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. k.chahed@yahoo.fr. 10. Faculté des Sciences de Sfax, Université de Sfax, Sfax, Tunisia. k.chahed@yahoo.fr.
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.
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-9C-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 COPDpatients 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 COPDpatients carrying the 279Q variant.
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