MMP-2 (-1306 C/T) Polymorphism Affects Serum Matrix Metalloproteinase (MMP)-2 Levels and Correlates with Chronic Obstructive Pulmonary Disease Severity: A Case-Control Study of MMP-1 and -2 in a Tunisian Population.

OBJECTIVE: The aim of this study was to determine the role of MMP-1 (-1607 1G/2G; -519 A/G) and MMP-2 (-1306 C/T; -735 C/T) polymorphisms in the development and severity of chronic obstructive pulmonary disease (COPD) in Tunisian patients. We also evaluated the impact of these genetic variants on serum levels of the corresponding proteins.

METHODS: The study included 138 patients with COPD and 216 healthy controls. Pulmonary function was evaluated using body plethysmography, and COPD severity was determined based on forced expiratory volume in 1 s (FEV1%). MMP-1 and MMP-2 variants were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), while serum matrix metalloproteinase (MMP)-1 and -2 levels were determined by enzyme-linked immunosorbent assay (ELISA) and activity of MMP-2 was determined by gelatin zymography.

RESULTS: No significant associations were found between genetic variations in MMP-1 and MMP-2 variants and the risk of development of COPD. Additionally, no significant impact of the MMP-1 (-1607 1G/2G; -519 A/G) and MMP-2 (-735 C/T) polymorphisms was observed on the respective protein levels and clinical parameters of the disease. Interestingly, a significant correlation was identified between the MMP-2 (-1306) C/T and disease severity [p = 0.01; Bonferroni corrected p value (p c ) = 0.04]. Increased levels of MMP-2 were also identified in patients with the MMP-2 (-1306) CC genotype compared with those with CT and TT genotypes (105 [84.69-121.5] vs. 86.29 [80.99-92.62] ng/ml; p = 0.01, p c  = 0.04). Additionally, MMP-2 activity was enhanced in patients carrying the CC genotype compared with those carrying the T variant (p = 0.01, p c  = 0.02).

CONCLUSION: Our data suggest that, although MMP-1 (-1607 1G/2G; -519 A/G) and MMP-2 (-735 C/T) may not affect COPD risk and clinical parameters, the MMP-2 (-1306C/T) variant was correlated to COPD severity. These findings could be related to alterations in the level and activity of MMP-2 in serum from patients carrying the (-1306) CC genotype.