The leucocyte telomere length, GSTM1 and GSTT1 null genotypes and the risk of COPD

Abstract

Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation and oxidative stress. The enhanced oxidative stress and inflammation have been reported to affect leucocyte telomere length (LTL). Glutathione S-transferase (GST) enzymes are a supergene family of phase II enzymes that utilize different ROS products. We aimed to explore the relation of <i>GSTM1</i> and <i>GSTT1</i> gene polymorphisms and LTL with COPD risk. For <i>GSTM1</i> we genotyped 152 COPD patients and 131 controls, and for <i>GSTT1</i>: 149 patients and 130 controls. Successful assessment of TL was performed for 91 patients and 88 controls. There was a significant difference in <i>GSTM1</i> null genotype frequency between the patients and controls (0.59 vs. 0.38, p≤0.000) but such wasn’t found for <i>GSTT1</i> (p=0.192). When combining both polymorphisms a significant prevalence of at least one null genotype among patients was observed (0.12 vs. 0.05, p=0.027). Association of <i>GSTT1</i> and LTL was not found.&nbsp; COPD patients caring <i>GSTM1</i> null genotype had shorter telomeres compared to non-null (15 720 bp vs. 22 442 bp, p=0.008) as in controls it was in opposite (31 354 bp vs. 17 800 bp, p=0.020). The significance in both groups remained when combining <i>GSTM1</i> and <i>GSTT1</i> (COPD at least one null: 16 409 bp vs. COPD non-null: 22 092 bp, p=0.029, and controls at least one null: 29 666 bp vs. controls non-null: 16 370 bp, p=0.027). The total glutathione in <i>GSTM1</i> non-null controls was higher compared to null (15.39 ng/ml vs. 5.53 ng/ml, p=0.002). In COPD patients we found no association (p=0.301). According to our results <i>GSTM1</i> but not <i>GSTT1</i> null genotypes might play role in leucocyte telomere shortening and thus be involved in the pathogenesis of COPD.