Glutathione S-transferase and microsomal epoxide hydrolase gene polymorphisms and risk of chronic obstructive pulmonary disease in Slovak population.
OBJECTIVE
To determine the risk of chronic obstructive pulmonary disease (COPD) associated with polymorphisms in the glutathione S-transferase (GST) M1, GST T1, and microsomal epoxide hydrolase (EPHX1) genes in a cohort of Slovak population.


METHODS
Two hundred and seventeen patients with the diagnosis of COPD and 160 control subjects were enrolled in the study. Blood samples were collected from all subjects and the DNA from peripheral blood lymphocytes was used for subsequent genotyping assays, using polymerase chain reaction and restriction fragment-length polymorphism methods.


RESULTS
In an unadjusted model, an increased risk for COPD was observed in subjects with EPHX1 His113-His113 genotype (odds ratio [OR], 2.32; 95% confidence interval [CI], 1.20-4.69; P=0.008), compared with the carriers of the Tyr113 allele. However, after the adjustments for age, sex, and smoking status, the risk was not significant (adjusted OR, 1.79; 95% CI, 0.91-3.53; P=0.093). In a combined analysis of gene polymorphisms, the genotype combination EPHX1 His113-His113/GSTM1 null significantly increased the risk of COPD in both, unadjusted (OR, 5.08; 95% CI, 1.70-20.43; P=0.001) and adjusted model (OR, 4.87; 95% CI, 1.57-15.13; P=0.006).


CONCLUSIONS
Although none of the tested gene polymorphisms was significantly related to an increased risk of COPD alone, our results suggest that the homozygous exon 3 mutant variant of EPHX1 gene in the combination with GSTM1 null genotype is a significant predictor of increased susceptibility to COPD in the Slovak population. The findings of the present study emphasize the importance of detoxifying and antioxidant pathways in the pathogenesis of COPD.
Zidzik
Jozef
J
Department of Medical Biology, School of Medicine, P. J. Safarik University, 040 66 Kosice, Slovakia. biomed1@lf.upjs.sk
Slabá
Eva
E
Joppa
Pavol
P
Kluchová
Zuzana
Z
Dorková
Zuzana
Z
Skyba
Peter
P
Habalová
Viera
V
Salagovic
Ján
J
Tkácová
Ruzena
R
D016022:Case-Control Studies; D004851:Epoxide Hydrolases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D029424:Pulmonary Disease, Chronic Obstructive / Q000201:enzymology* / Q000453:epidemiology; D012307:Risk Factors; D018154:Slovakia / Q000453:epidemiology
D005982:Glutathione Transferase; D004851:Epoxide Hydrolases