Genetic Polymorphism in Matrix Metalloproteinase 9 in Chronic Obstructive Pulmonary Disease in Sohag University Hospital.

Genetic Polymorphism in Matrix Metalloproteinase 9 in Chronic Obstructive Pulmonary Disease in Sohag University Hospital.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous and complex disease with multiple clinical presentations or phenotypes and remains a highly prevalent condition, causing significant morbidity and mortality worldwide.

Chronic obstructive pulmonary disease (COPD) is the third most common cause of global mortality, affecting over 210 million individuals.

Chronic obstructive pulmonary disease (COPD) is a chronic airway disease involving chronic local and systemic inflammatory changes, clinically characterized by continuous and progressive airflow obstruction with airway remodeling and lung parenchyma destruction as pathological basis.

The precise molecular mechanism underlying the pathogenesis of COPD remains unclear ( Zhang J. et al., 2021). At present, it is generally believed that several risk factors are directly related to the pathogenesis of COPD, including host and environmental factors .

Among environmental factors, smoking, exposure to chemicals, indoor and outdoor air pollution are risk factors for COPD.

Host factors of COPD include antitrypsin-1, excessive deposition of extracellular matrix (ECM), corticosteroids, inflammatory stimuli, and metabolic imbalances .

Matrix metalloproteinases (MMPs) is a family of calcium- and zinc-dependent proteinase. There are currently at least 26 subtypes that can degrade almost all extracellular matrix and basement membrane components .

The MMP-9 gene is located on human chromosome 16, including 13 exons and 12 introns and its regulation mainly occurs at the transcriptional level. In the pathogenesis of COPD, MMP-9 mainly degrades the extracellular matrix and basement membrane of alveolar wall, destroying the normal structure of lung tissue. At the same time, MMP-9 also repairs the extracellular matrix and participates in respiratory tract reconstruction.

In addition, MMP-9 can also participate in inflammatory response, causing inflammatory cells to accumulate in the airway, thus increasing airway responsiveness. Study found that MMP-9 is highly expressed in the lung tissues of COPD patients and leads to generation of sputum. MMPs are important in COPD. They degrade matrix proteins (elastin, collagen) during the disease progression .

Therefore the analysis of MMP-9 gene polymorphism is an important starting point to explore the susceptibility to COPD. It has been found that there is a mutation from C to T at site 1562 of promoter MMP-9, which may affect the expression level of MMP-9 gene. The MMP-9-C1562T polymorphism is an important reason for the abnormal increase of MMP-9 expression level .

Inclusion Criteria:

chronic respiratory symptom and signs such as cough ,breathlessness , wheeze ; forced expiratory volume in one second(FEV1)of predicted (FEV1%) less than 80 % ; the ratio of FEV1 to forced vital capacity (FVC , FEV1/ FVC)<70 % ; FEV1reversibility after inhalation of 200g salbutamol (bronchodilator) of less than 12 % of prebronchodilator FEV1.

Exclusion Criteria:

Coexistence of asthma and COPD or with earlier history of bronchial asthma as well as patients who have never smoked were excluded from the study.

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