Association between cytochrome P450 3A5 polymorphism and the lung function in Saskatchewan grain workers.
OBJECTIVE
The activity of the enzymes that metabolize tobacco smoke may affect the susceptibility to chronic obstructive pulmonary disease (COPD). Cytochrome P450 (CYP) 3A5 is expressed selectively over CYP3A4 in human lung, but the association between the CYP3A5 polymorphisms and the airway injury is unknown.


METHODS
Two hundred and six male Saskatchewan grain workers participated in this longitudinal study, and their lung function values of forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC), respiratory symptoms, smoking status, and the occupational history were analyzed.


RESULTS
A significant interactive effect was observed between the CYP3A5 genotype and current smoking status on FEV1, and the annual decline rates of FEV1 and FVC in current smokers were greater among CYP3A5*1/*3 carriers than CYP3A5*3/*3 carriers (-48.7+/-16.4 vs. -31.5+/-4.7 ml/years, P=0.02; -27.4+/-18.9 vs. -5.8+/-6.5 ml/years, P=0.04). The incidences of chronic cough and COPD were also higher in current smokers with CYP3A5*1/*3 than in nonsmokers and current smokers with CYP3A5*3/*3. The adjusted odds ratios for chronic cough and COPD current smokers with CYP3A5*1/*3 versus nonsmokers with the CYP3A5*3/*3 genotype were 11.4 (P=0.009) and 4.3 (P=0.13), respectively.


CONCLUSIONS
The results suggest that CYP3A5*1 may be a novel genetic risk factor for airway injury in smokers, and that CYP3A5 may play a role in airway injury owing to the bioactivation of chemicals in tobacco smoke.
Seo
Takayuki
T
Division of Pharmacology and Therapeutics, Graduate School of Medical and Pharmaceutical Science, Kumamoto University, Kumamoto, Japan.
Pahwa
Punam
P
McDuffie
Helen H
HH
Yurube
Keigo
K
Egoshi
Masayoshi
M
Umemoto
Yuichiro
Y
Ghosh
Sunita
S
Fukushima
Yumi
Y
Nakagawa
Kazuko
K
D000328:Adult; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D004391:Dust; D002523:Edible Grain; D005541:Forced Expiratory Volume; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D016273:Occupational Exposure; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D029424:Pulmonary Disease, Chronic Obstructive / Q000201:enzymology / Q000209:etiology* / Q000235:genetics* / Q000503:physiopathology; D012129:Respiratory Function Tests; D012307:Risk Factors; D012525:Saskatchewan; D012907:Smoking / Q000009:adverse effects; D014797:Vital Capacity
D004391:Dust; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A