الفهرس 
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
Risk Factors for COPDOnly 14 pages are availabe for public view
 |  | from | 138 |  |  |
| | | from | 138 | | |
Abstract
Chronic obstructive pulmonary disease (COPD) is a group of progressive, debilitating respiratory conditions, including emphysema and chronic bronchitis, characterized by difficult breathing, lung airflow limitations, cough, and other symptoms. COPD is expected to be the third leading cause of worldwide mortality and the fifth leading cause of morbidity by the year 2020.
Almost by definition, tobacco use is by far the most important risk factor for COPD. However, not all heavy smokers develop COPD and there has been considerable interest in other risk factors. Dusty occupational environments are well established risks. Childhood respiratory illnesses may render some people susceptible to tobacco-induced lung damage. All of these influences are minor compared to that of smoking and none satisfactorily explains the differences between smokers who develop COPD and those who do not, suggesting the influence of genetic factors on COPD susceptibility.
The detoxification and oxidative stress pathways that determine the susceptibility to COPD progression are poorly understood especially at the genetic and phenotypic concentrations. Increased oxidative burden, which plays a major role in the pathogenesis of COPD is caused either directly, as a result of smoking, or indirectly by the release increasing amount of reactive oxygen species (ROS) from airways leukocytes and other inflammatory cells. Polymorphism of antioxidant genes may also lead to increased oxidative stress and subsequent inflammatory response, thereby leading to gradual loss of lung function in smokers.
The cytochrome p450 (CYP) enzymes, which represent a large multigene family with different substrate specificities, are important in phase I detoxification reactions. The CYP1A1 gene product, aromatic hydrocarbon hydroxylase catalyzes the first oxidative step in the metabolism of polycyclic aromatic hydrocarbons (PAH) that are found in tobacco smoke. The reactive intermediates produced are significantly more toxic than their parent compounds.
Since the complexity of the disease results from both gene–gene and gene–environment interactions, and tobacco smoke is a known environmental factor causing the disease, the genetic polymorphisms of detoxifying and oxidative stress-related genes are expected to be important markers in individual susceptibility. Among the several single nucleotide polymorphisms (SNPs) of CYP1A1 gene, is the MspI polymorphism, which is T to C substitution at 3801 nucleotide in the 3′ non-coding region, have been associated with increased enzyme activity.
Our study aimed to evaluate the role of Cytochrome P450 1A1 (CYP1A1 MspI) (3801 T/C) gene polymorphism in the development of chronic obstructive pulmonary disease (COPD).
This study was conducted on 35 COPD patients who were recruited from inpatient ward and outpatient clinic of Chest Department of Ain Shams University Hospitals and 15 age- and sex- matched, apparently healthy, non smoker individuals with no history or clinical findings suggestive of chest diseases. Assay of MspI gene polymorphism was performed by PCR-RFLP analysis.
Our results showed no significant statistical difference in the genotypic distributions of the CYP1A1 MspI SNP between COPD patients and the control subjects. However, we observed a significant association between the presence of C allele and development of more severe COPD cases.
In conclusion, the study had demonstrated that there was no significant association between CYP1A1 MspI gene polymorphism and risk of development of COPD in Egyptian population. The non-significance of our results in this study may be due to the small sample size compared to other studies, ethnic variation and different population.