Background and Objectives-The chronic obstructive pulmonary disease (COPD) is the progressive inflammatory disease including airways, alveoli, and the pulmonary vasculature, ultimately leading to the irreversible airflow limitation, and loss of the elastic recoil. to investigate the gene expression, genetic expression of IL-4, IL-13, and gene expression of MMP-9 in the genetic predisposition of COPD and their correlation with the its severity and progression Methods- It was a Prospective Case Control Study conducted at Department of Anatomy along with Department of Pathology and Genetics, Subharti Medical College (SMC), Meerut, U.P. in collaboration with Department of Respiratory Medicine, Prasad Institute of Medical Sciences (PIMS), Lucknow. After taking the ethical clearance from the ethical committee of SMC volunteers having COPD was identified as subjects and asymptomatic volunteers as controls for the proposed study. A written informed consent was obtained from the volunteers prior to enrolling in the study. We were need to study 149 COPD patients and 149 healthy controls to be able to reject the Null hypothesis that the mean ratio of the COPD group and healthy control groups are equal with a probability (power 0.8). A total of 300 people were selected as the sample size for the purpose of this study. The study participants were divided into two groups Results- there was significant gene expression in all biomarkers in both cases and controls (p<0.05). The mean gene expression of IL4 cases: controls (16.3±3.2: 12.3±3.2) for IL 13 (82.6±7.5: 51.8±6.0) and MMP-9 (300.8±20: 249.8±11.8) were all significant. The data reveal a positive correlation, as the severity increases from GOLD I to GOLD IV, so do the expression levels of IL4 (from 2.1 to 3.2 CT value) and IL13 (from 1.5 to 2.9) and MMP-9 (from 1.3 to 2.8). Conclusion- The identification of genetic expressions associated with COPD susceptibility and the characterization of gene expression profiles linked to disease severity provide valuable targets for future research and therapeutic interventions. Understanding the molecular mechanisms underlying COPD is crucial for developing personalized treatment strategies and improving patient outcomes.