A study on the correlation of matrix metalloproteinase MMP1 in COPD and smoking in the North Indian population

Abstract

Background: Chronic Obstructive Pulmonary Disease (COPD) is characterized by airway obstruction and destruction of lung tissue, the disease for which at present there is no cure, although the treatment can slow worsening. Nearly 90% of COPD is caused by long term cigarette smoking; however, only 25% of chronic tobacco smokers develop COPD, the exact cause of this predisposition of some smokers to acquire COPD is still poorly understood at the molecular level. Lot of studies are available showing the correlation of MMP1 and asthma but not much work has been done on its correlation with COPD especially in North India. The outcome of our study was also expected to discover MMP1 as a new target for treating COPD and its progression in smokers. Aims and Objectives: The association of COPD and smoking with MMP1 gene product and SNP in the North Indian population was intended to be studied. Material and Methods:The proposed study was a case control study. In this study adults aged 30 years and above fulfilling the inclusion criteria (the criteria mentioned under the materials and methods) were considered and a total of 180 subjects were taken after determining the sample size. Pulmonary function test (PFT) was performed by Spirometry. Three main groups each consisting of 60 subjects were formed on the basis of smoking history and Spirometry: Ist group: Smokers without co-morbidity with normal PFT, IInd group: Smokers with Spirometry proved COPD and without any other co-morbidity, IIIrd group: Healthy Non-smoker controls. Quantification of metalloproteinase MMP1 in all the groups were performed in the serum with ELISA kits and Single Nucleotide Polymorphism (SNP 1G-1607 2G, ID rs1799750) studiesin the gene encoding MMP1 linked to COPD susceptibility in smokers was performed by DNA Sequencing Analysis. The correlation between the SNPs, gene product, smokingand COPD was studied. Results: MMP1 concentration was seen increased in serum of COPD and smokers when compared to healthy controls. And there is high negative correlation between *FEV1/FVC % (post-bronchodilator)and MMP1 in COPD compared to Smokers and Healthy Controls. However, from the results of present analysis, we could show negative correlation between MMP1 and *FEV1/FVC % in all the 3 groups but the correlation proves to be much more negative in Group II i.e. Smokers with COPD. Statistically Significant Positive Correlation of Pack Years with MMP1 conc., and Statistically Significant Negative Correlation between Pack Years and *FEV1/FVC % was seen. Conclusion: In conclusion, our present analyses did show significant association between MMP1 and COPD risk in North Indian population. MMP1 levels of COPD patients were significantly increased in smokers and may contribute to or be a marker of the pathophysiology of COPD.

Clinical features of chronic bronchitis and genetic risk factors for the development of chronic obstructive pulmonary disease in adolescent smokers

“…This causes an increase in the enzymatic activity of MMP-1 in lung epithelial cells and disrupts the balance in the protease-antiprotease system. MMP-1 hypersecretion causes destruction of Type III collagen and leads to the formation of emphysema [13].…”

cAMP-PDE signaling in COPD: Review of cellular, molecular and clinical features

“…Matrix Metalloproteinases (MMPs) play pivotal roles in lung development and repair processes [ 70 ]. This zinc-dependent protease family consists of 24 endopeptidases that are important in lung inflammatory diseases such as asthma and COPD.…”

“…The imbalance of protease (MMPs) and antiproteases (TIMP-1) is the hallmark of COPD that involved in immune cell infiltration and migration and tissue destruction. For instance, serum level of MMP1 is significantly higher in COPD patients compared to healthy control [ 70 ]. Accordingly, blockade of MMP1 using Duloxetine, a selective serotonin reuptake inhibitor, resulted in decreased levels of TLR4 and IL8, and prevented alveolar tissue damage [ 71 ].…”