Sarra Bchir1,2, Hela Ben Nasr1,3, Abdelhamid Garrouch4, Amel Ben Anes1, Ammar Abbassi1,5, Zouhair Tabka1, Karim Chahed1,6. 1. Unité de recherche UR12ES06, Physiologie de l'Exercice et Physiopathologie: de l'Intégré au Moléculaire 'Biologie, Médecine et Santé', Université de Sousse, Faculté de Médecine de Sousse, Tunisia. 2. Department of Biology, Institut Supérieur de Biotechnologie de Monastir, Université de Monastir, Tunisia. 3. Department of Biology, Institut des Sciences Infirmières, Sousse, Tunisia. 4. Service de Pneumo-Allergologie, CHU Farhat Hached, Sousse, Tunisia. 5. District Medical du Centre, CNAM, Sousse, Tunisia. 6. Department of Biochemistry, Université de Sfax, Faculté des Sciences de Sfax, Tunisia.
Abstract
BACKGROUND: The present study aimed to examine the role of matrix metalloproteinase (MMP)-3 [(-1171) 5A/6A; Lys45Glu (A/G)], MMP-7 [(-181) A/G] and MMP-12 [(-82) A/G; Asn357Ser (A/G)] variants in the development and severity of chronic obstructive pulmonary disease (COPD) in Tunisians. METHODS: Plethysmography was performed in all participants to measure forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC parameters. Genotyping of MMP-3, MMP-7 and MMP-12 polymorphisms was carried out in 138 patients with COPD and 216 healthy controls using a polymerase chain reaction-restriction fragment length polymorphism. Serum levels of MMPs and cytokines (interleukin-6, tumor necrosis factor-α) were determined by an enzyme-linked immunosorbent assay. RESULTS: No significant correlations were observed between genetic variations in MMP-3, MMP-7 and MMP-12 and the risk of development of COPD. Additionally, no impact of MMP-7 (-181) A/G and MMP-12 [(-82) A/G; Asn357Ser (A/G)] polymorphisms was observed on the respective protein levels and clinical parameters of the disease. Interestingly, both MMP-3 (-1171) 5A/6A and Lys45Glu (A/G) variants were associated with respiratory function, as well as with serum levels of MMP-3 in COPD patients. A relationship was found between the (-1171) 6A and 45Glu (G) alleles of the MMP-3 gene and enhanced airflow limitation among COPD patients. Additionally, carriers of the 6A6A and 45 GG genotypes present higher MMP-3 levels than noncarriers. CONCLUSIONS: MMP-3 (-1171) 5A/6A and Lys45Glu (A/G) polymorphisms were associated with the decline of lung function among COPD patients. These results could be linked to the upregulation of MMP-3 in serum from COPD patients carrying the (-1171) 6A and 45 G homozygous genotypes.
BACKGROUND: The present study aimed to examine the role of matrix metalloproteinase (MMP)-3 [(-1171) 5A/6A; Lys45Glu (A/G)], MMP-7 [(-181) A/G] and MMP-12 [(-82) A/G; Asn357Ser (A/G)] variants in the development and severity of chronic obstructive pulmonary disease (COPD) in Tunisians. METHODS: Plethysmography was performed in all participants to measure forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC parameters. Genotyping of MMP-3, MMP-7 and MMP-12 polymorphisms was carried out in 138 patients with COPD and 216 healthy controls using a polymerase chain reaction-restriction fragment length polymorphism. Serum levels of MMPs and cytokines (interleukin-6, tumor necrosis factor-α) were determined by an enzyme-linked immunosorbent assay. RESULTS: No significant correlations were observed between genetic variations in MMP-3, MMP-7 and MMP-12 and the risk of development of COPD. Additionally, no impact of MMP-7(-181) A/G and MMP-12 [(-82) A/G; Asn357Ser (A/G)] polymorphisms was observed on the respective protein levels and clinical parameters of the disease. Interestingly, both MMP-3 (-1171) 5A/6A and Lys45Glu (A/G) variants were associated with respiratory function, as well as with serum levels of MMP-3 in COPDpatients. A relationship was found between the (-1171) 6A and 45Glu (G) alleles of the MMP-3 gene and enhanced airflow limitation among COPDpatients. Additionally, carriers of the 6A6A and 45 GG genotypes present higher MMP-3 levels than noncarriers. CONCLUSIONS:MMP-3 (-1171) 5A/6A and Lys45Glu (A/G) polymorphisms were associated with the decline of lung function among COPDpatients. These results could be linked to the upregulation of MMP-3 in serum from COPDpatients carrying the (-1171) 6A and 45 G homozygous genotypes.
Authors: Martina Sundqvist; Kristina Andelid; Ann Ekberg-Jansson; Johan Bylund; Anna Karlsson-Bengtsson; Anders Lindén Journal: Int J Chron Obstruct Pulmon Dis Date: 2021-02-19