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GSTP1, GSTM1 and GSTT1 genotypes and serum GST in male COPD

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by breathing difficulties, wheezing and chronic cough and defined by expiratory airflow (FEV1) limitation. It has generally been accepted that cigarette smoking represents the most important risk factor favouring COPD onset. The fact that only 10% to 20% of chronic smokers develop severe COPD-related pulmonary function impairment indicates the presence of genetic predisposing factors involved into COPD pathogenesis. The aim of the study was to determine the genotype distribution for the GSTP1 A313G exon 5 polymorphism, GSTP1 C341T exon 6 polymorphism and deletions in GSTM1 and GSTT1 genes in samples of 90 subjects (COPD and controls) and to investigate the association between GST polymorphisms and COPD. Serum GST activity was evaluated as a distinguishable biochemical marker of the disease presence/absence. Also, in order to confirm the presence of an inflammatory process in COPD subjects, serum alpha-1-antitrypsin (AAT) concentration was determined. Lactate dehydrogenase (LDH) activity was determined in order to test for an increased anaerobic metabolism in COPD. The A313G and C341T GSTP1 genotypes were determined by PCR-RFLP, GSTM1 and GSTT1 deletions by a multiplex PCR, GST activity using spectrophotometric method, LDH and AAT by standard methods in older male Caucasian Croats with stable COPD (n=30) and sex/age matched controls (n=60 ; non-smokers, ex-smokers, and smokers). The differences in GSTP1 exon 5, GSTP1 exon 6 and allele frequencies (A/G and C/T) found in the control and COPD group were statistically significant (p<0.05). Of statistical significance, CC/TT odds ratio equalled to 10.000 (p<0.05). The frequency of null GSTM1, null GSTT1 and the two lacked statistical significance (p>0.05). Total GST did not statistically differ either between the controls and COPD patients, or across smoking-based subgroups. The differences in total AAT concentrations and LDH activities seen across the two studied groups reached statistical significance (p<0.05). A statistically significant differences were obtained for AAT (control non-smokers vs. the entire COPD arm, p<0.05) and for LDH activity registered in the control vs. COPD non-smokers (p<0.05). The results of serum AAT concentration confirmed the existence of inflammation and elevated LDH activity chronic hypoxia in stable male COPD patients. Our study showed AA and CC genotypes to be COPD-protective, and AG/GG and CT/TT to be COPD-risky. Null GSTM1, null GSTT1 and the two were not proven disease-associated. Serum GST and smoking status were proven mutually independent. Serum GST lacks sufficient power to discriminate between stable COPD and COPD-free individuals.

COPD; GST genotypes; serum GST concentration

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