COX2 and p53 risk-alleles coexist in COPD
Ehtesham Arif1, Arpana Vibhuti, Desh Deepak
1Functional Genomics Unit, Institute of Genomics and Integrative Biology, Delhi, India.
Summary
Genetic variations in COX2 and p53 influence susceptibility to Chronic Obstructive Pulmonary Disease (COPD). Specific COX2 and p53 risk-alleles and their combinations are associated with increased COPD risk.
Area of Science:
- Genetics
- Pulmonology
- Molecular Biology
Background:
- Cigarette smoke triggers pro-inflammatory cytokines from airway epithelial cells, affecting inflammation-related genes like COX2.
- p53 expression is altered in response to cigarette smoke, and it shares functions with COX2 in inflammation and oxidative stress.
Purpose of the Study:
- To investigate the role of cyclooxygenase-2 (COX2) and p53 gene polymorphisms in susceptibility to Chronic Obstructive Pulmonary Disease (COPD).
- To examine within-gene and gene-gene interactions of COX2 and p53 in relation to COPD risk.
Main Methods:
- A prospective gene-association study was conducted using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) for genotyping.
- COX2 (-765G/C and 8473T/C) and p53 (72Pro/Arg) polymorphisms were analyzed in 229 COPD patients and 147 healthy controls.
Main Results:
- Specific COX2 (-765GC+CC) and p53 (Pro/Pro+Pro/Arg) genotypes showed higher prevalence in COPD patients, indicating increased odds ratios.
- The -765C and 72Pro alleles were identified as risk-alleles. A significant association was found for the COX2 -765C:8473C haplotype.
- Combinations of genotypes with multiple risk alleles (3, 4, or 5) were over-represented in patients, while combinations with fewer risk alleles were prevalent in controls.
Conclusions:
- The study concludes that the prevalence of specific COX2 and p53 risk-alleles contributes significantly to COPD susceptibility.
- Gene-gene interactions and combinations of risk alleles reinforce the association with disease risk.
Related Concept Videos
01:20COPD: Pathogenesis and Clinical Features
Chronic obstructive pulmonary disease (COPD) is a group of lung conditions that progressively worsen over time, including chronic bronchitis and emphysema. This cluster of diseases collectively leads to a gradual and irreversible decline in lung function over time.
The primary cause for the onset of COPD is cigarette smoking and exposure to air pollution. These hazardous factors initiate a chain reaction within the lungs, resulting in chronic inflammation, damage to the airways, and a...
The primary cause for the onset of COPD is cigarette smoking and exposure to air pollution. These hazardous factors initiate a chain reaction within the lungs, resulting in chronic inflammation, damage to the airways, and a...
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
01:20Chronic Obstructive Pulmonary Disease-II: Pathophysiology
Chronic Obstructive Pulmonary Disease (COPD) pathophysiology is intricate and multifaceted, involving a complex interplay of physiological processes. Understanding these mechanisms is crucial for effectively managing and treating COPD. Here is an in-depth look at the critical elements in the pathophysiology of COPD:
Chronic Inflammation
Chronic Inflammation
01:23Chronic Obstructive Pulmonary Disease I: Introduction
Chronic obstructive pulmonary disease is a common, preventable, and treatable respiratory disorder characterized by persistent symptoms and progressive airflow limitation. This limitation results from a combination of small-airway disease (obstructive bronchiolitis) and parenchymal destruction (emphysema), both driven by chronic inflammation from exposure to harmful particles or gases.The disease includes two main pathological entities: emphysema, marked by destruction of alveolar walls and...
01:24Chronic Obstructive Pulmonary Disease
COPD is defined as a heterogeneous lung condition marked by persistent respiratory symptoms such as dyspnea, cough, and sputum production, caused by abnormalities in the airways that cause airflow obstruction.
Smoking is a primary risk factor for COPD, with over 80% of patients having a history of it. Patients typically experience progressive dyspnea or labored breathing, frequent coughing, and recurrent pulmonary infections. Many eventually succumb to respiratory failure, characterized by...
Smoking is a primary risk factor for COPD, with over 80% of patients having a history of it. Patients typically experience progressive dyspnea or labored breathing, frequent coughing, and recurrent pulmonary infections. Many eventually succumb to respiratory failure, characterized by...
01:20Chronic Obstructive Pulmonary Disease-I: Introduction
Chronic Obstructive Pulmonary Disease (COPD) is a long-lasting respiratory condition requiring continuous attention and care. It is a progressive lung disease that leads to breathing challenges due to airflow obstruction. It manifests as persistent respiratory symptoms and restricted airflow resulting from abnormalities in the airways and alveoli, usually due to long-term exposure to harmful particles or gases. COPD mainly consists of two primary conditions: emphysema and chronic bronchitis.