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Molecular diagnosis & therapy

Matrix Metalloproteinase-9 (279R/Q) Polymorphism is Associated with Clinical Severity and Airflow Limitation in Tunisian Patients with Chronic Obstructive Pulmonary Disease.


PMID 26303146

Abstract

The aim of this study was to investigate the role ofxa0matrix 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. Pulmonary functional tests were evaluated by body plethysmography. MMP-9 genotypes were determined in patients withxa0COPDxa0(nxa0=xa0138) and healthy controls (nxa0=xa0216) 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. 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 279xa0R/Q polymorphism and disease severity (Pxa0=xa00.02). In addition, homozygous Q (A) genotype was associated with a poorer lung function with a fall in forced expiratory volume in 1xa0s (FEV1) (%) and forced vital capacity (FVC%) among COPD patients compared with both AG and GG individuals (52.06xa0±xa019.6 vs. 59.08xa0±xa017.19, Pxa0=xa00.03 and 72.41xa0±xa021.42 vs. 82.98xa0±xa016.48, Pxa0=xa00.002, respectively). Using ELISA, a higher level of MMP-9 was found in patients with the CT genotype (Pxa0=xa00.03), while no significant impact of the 279R/Q polymorphism was observed (Pxa0=xa00.48). 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 (Pxa0=xa00.02). 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.