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MMP-3 (-1171 5A/6A; Lys45Glu) variants affect serum levels of matrix metalloproteinase (MMP)-3 and correlate with severity of COPD: a study of MMP-3, MMP-7 and MMP-12 in a Tunisian population.

MMP-3 (-1171 5A/6A; Lys45Glu) variants affect serum levels of matrix metalloproteinase (MMP)-3 and correlate with severity of COPD: a study of MMP-3, MMP-7 and MMP-12 in a Tunisian population.
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Bchir S, Ben Nasr H, Garrouch A, Ben Anes A, Abbassi A, Tabka Z, Chahed K,


Bchir S, Ben Nasr H, Garrouch A, Ben Anes A, Abbassi A, Tabka Z, Chahed K, (click to view)

Bchir S, Ben Nasr H, Garrouch A, Ben Anes A, Abbassi A, Tabka Z, Chahed K,

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The journal of gene medicine 2017 11 22() doi 10.1002/jgm.2999
Abstract
OBJECTIVE
The goal of this study was to examine the role of 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 FEV1, 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 polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Serum levels of MMPs and cytokines (IL-6, TNF-α) were determined by enzyme-linked immunosorbent assay (ELISA).

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 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 non carriers.

CONCLUSION
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 45G homozygous genotypes.

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