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Association between cytochrome P450 3A5 polymorphism and the lung function in Saskatchewan grain workers
Takayuki Seo1, Punam Pahwa, Helen H McDuffie
1Division of Pharmacology and Therapeutics, Graduate School of Medical and Pharmaceutical Science, Kumamoto University, Kumamoto, Japan.
Pharmacogenetics and Genomics
|May 23, 2008
Summary
Genetic variations in Cytochrome P450 (CYP) 3A5 influence susceptibility to chronic obstructive pulmonary disease (COPD). The CYP3A5*1 allele is a risk factor for airway injury in smokers.
Area of Science:
- Pulmonary Medicine
- Genetics
- Environmental Health
Background:
- Tobacco smoke exposure is a primary risk factor for chronic obstructive pulmonary disease (COPD).
- Enzymes metabolizing tobacco smoke components, such as Cytochrome P450 (CYP) 3A5, may modulate COPD susceptibility.
- CYP3A5 is preferentially expressed in the human lung, but its role in smoking-related airway injury is not well understood.
Purpose of the Study:
- To investigate the association between Cytochrome P450 (CYP) 3A5 genetic polymorphisms and airway injury in male grain workers.
- To determine if CYP3A5 genotype influences lung function decline and the risk of respiratory symptoms and COPD in smokers.
Main Methods:
- A longitudinal study of 206 male grain workers was conducted.
- Lung function parameters (FEV1, FVC), respiratory symptoms, smoking status, and occupational history were analyzed.
- CYP3A5 genotypes were assessed and correlated with clinical outcomes.
Main Results:
- A significant interaction was found between CYP3A5 genotype and smoking status on forced expiratory volume in the first second (FEV1).
- Current smokers with the CYP3A5*1/*3 genotype exhibited greater annual decline rates in FEV1 and FVC compared to CYP3A5*3/*3 carriers.
- Higher incidences of chronic cough and COPD were observed in current smokers carrying the CYP3A5*1/*3 genotype.
Conclusions:
- The CYP3A5*1 allele may represent a novel genetic risk factor for smoking-induced airway injury.
- CYP3A5 likely plays a role in airway damage through the bioactivation of chemicals present in tobacco smoke.
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