engleski

Frequency of Q192R, L55M and -108C>T polymorphisms of pon1 and S311C polymorphism of pon2 gene in chronic obstructive pulmonary disease: The Croatian study

Chronic obstructive pulmonary disease (COPD) is characterized by chronic local and systemic inflammation, and increased oxidative stress. The paraoxonase (PON) gene family includes three members (pon1, pon2, pon3). Paraoxonase 1 (PON1) is a HDL- associated enzyme which participates in lipid metabolism. It has been shown that polymorphisms in coding (Q192R, L55M) and promoter regions (-108C>T) of pon1 gene affect PON1 activity. Paraoxonase 2 (PON2) is ubiquitously expressed in nearly all human tissues and acts as cellular antioxidant. S311C is a common polymorphism of pon2 gene and it has been reported to be associated with the high risk of atherosclerosis. The aim of this study was to determine the frequency of Q192R, L55M and -108C>T polymorphisms of pon1 gene and S311C polymorphism of pon2 gene as well as to assess the association of polymorphisms of pon1 gene and the level of PON1 activity in COPD. The study was carried out on 107 COPD patients (32 smokers, 28 ex-smokers, 47 non-smokers) and 45 healthy volunteers (16 smokers, 13 ex-smokers, 16 non-smokers). Polymorphisms were determined by PCR-RFLP procedure. PON1 activity was assayed with paraoxon (in absence and in the presence of NaCl) and phenylacetate as substrates. Basal and salt-stimulated paraoxonase PON1 activity alone and standardized with HDL concentration were significantly reduced in COPD patients as compared with controls (P<0.05). In addition, arylesterase PON1 activity alone and standardized with HDL or apoAI concentration was also significantly lower in COPD patients (P<0.001). The analysis of pon1 gene polymorphisms in COPD patients showed following distribution of genotypes: 71% QQ, 25% QR and 4% RR for Q192R ; 45% LL, 42% LM and 13% MM for L55M ; 15% CC, 42% CT and 43% TT for -108 C>T. In the control group we found different distribution of genotypes for Q192R: 89% QQ, 7% QR, 4% RR (P<0.05) and for -108 C>T: 38% CC, 49% CT and 13% TT (P<0.001), while distribution of genotypes for L55M was similar to COPD group (60% LL, 35% LM and 5% MM). The analysis of pon2 gene S311C polymorphism showed following distribution of genotypes in COPD patients: 55% SS, 32% SC and 13% CC, which was similar to distribution of genotypes in control group (61% SS, 18% SC and 21% CC). Our results suggest that Q192R and -108C>T pon1 gene polymorphisms may be associated with lower PON1 paraoxonase and arylesterase activity in COPD patients in Croatian population.

pon1 ; pon2 ; chronic obstructive pulmonary disease ; polymorphisms

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