title: Matrix Metalloproteinase-9 (279R/Q) Polymorphism is Associated with Clinical Severity and Airflow Limitation in Tunisian Patients with Chronic Obstructive Pulmonary Disease.
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).
  
  
  CONCLUSIONS
  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.
authors: 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.|Institut Supérieur de Biotechnologie de Monastir, Université de Monastir, Monastir, Tunisia.
authors: Sarra
authors: S
authors: Bchir
authors: 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.|Institut des Sciences Infirmières, Sousse, Tunisia.
authors: Hela Ben
authors: HB
authors: Nasr
authors: Laboratoire de Biotechnologie, Faculté des Sciences de Sfax, Sfax, Tunisia.
authors: Imen Rekik
authors: IR
authors: Hakim
authors: 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.|Faculté des Sciences de Bizerte, Université de Carthage, Tunis, Tunisia.
authors: Amel Ben
authors: AB
authors: Anes
authors: Unité de Recherche "UR06SP05" Centre Régional de Transfusion Sanguine, CHU Farhat Hached, Sousse, Tunisia.
authors: Saloua
authors: S
authors: Yacoub
authors: Service de Pneumo-Allergologie, CHU Farhat Hached, Sousse, Tunisia.
authors: Abdelhamid
authors: A
authors: Garrouch
authors: Service de Pneumo-Allergologie, CHU Farhat Hached, Sousse, Tunisia.
authors: Mohamed
authors: M
authors: Benzarti
authors: INSERM U1138, Université Pierre et Marie Curie, Université Paris-Descartes, Centre de Recherche des Cordeliers, Paris, France.
authors: Brigitte
authors: B
authors: Bauvois
authors: 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.
authors: Zouhair
authors: Z
authors: Tabka
authors: 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.|Faculté des Sciences de Sfax, Université de Sfax, Sfax, Tunisia. k.chahed@yahoo.fr.
authors: Karim
authors: K
authors: Chahed
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D004795:Enzyme Stability; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000737:chemistry / Q000235:genetics*; D008875:Middle Aged; D008958:Models, Molecular; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D012123:Pulmonary Ventilation; D012720:Severity of Illness Index; D014416:Tunisia
chemical_list: C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9