Original scientific paper
Glutathione S-transferase and Microsomal Epoxide Hydrolase Gene Polymorphisms and Risk of Chronic Obstructive Pulmonary Disease in Slovak Population
Jozef Židzik
; Department of Medical Biology, Medical Faculty, P. J. Šafarik University, Košice, Slovakia
Eva Slabá
; Department of Medical Biology, Medical Faculty, P. J. Šafarik University, Košice, Slovakia
Pavol Joppa
; Department of Respiratory, Disordes and Tuberculosis, Medical Faculty, P.J. Šafarik University and L. Pasteur Teaching Hospital, Košice, Slovakia
Zuzana Kluchová
; Department of Respiratory, Disordes and Tuberculosis, Medical Faculty, P.J. Šafarik University and L. Pasteur Teaching Hospital, Košice, Slovakia
Zuzana Dorková
; Department of Respiratory, Disordes and Tuberculosis, Medical Faculty, P.J. Šafarik University and L. Pasteur Teaching Hospital, Košice, Slovakia
Peter Skyba
; Department of Respiratory, Disordes and Tuberculosis, Medical Faculty, P.J. Šafarik University and L. Pasteur Teaching Hospital, Košice, Slovakia
Viera Habalová
; Department of Medical Biology, Medical Faculty, P. J. Šafarik University, Košice, Slovakia
Ján Šalagovič
; Department of Medical Biology, Medical Faculty, P. J. Šafarik University, Košice, Slovakia
Ružena Tkáčová
; Department of Respiratory, Disordes and Tuberculosis, Medical Faculty, P.J. Šafarik University and L. Pasteur Teaching Hospital, Košice, Slovakia
Abstract
Aim 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).
Conclusion 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.
Keywords
Chronic obstructive pulmonary disease; Glutathione S-transferase; Microsomal epoxide hydrolase, Gene polymorphism
Hrčak ID:
26108
URI
Publication date:
15.4.2008.
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