engleski

Q192R and L55M polymorphisms of PON1 are not related with chronic renal failure

Paraoxonase (PON), an HDL-associated enzyme, is believed to contribute to the protective effects of HDL by decreasing generation of lipid peroxide during process of LDL oxidation. Molecular basis for variation in PON1 activity appears to be related to the polymorphisms of pon1 gene. Two common polymorphisms of pon1 gene (Q192R and L55M) have been associated with the high risk of atherosclerosis. We carried out this study in order to determine frequencies of Q192R and L55M polymorphisms and PON1 activity in patients with chronic renal failure undergoing hemodialysis. It is well known that these patients may have an increased risk of developing atherosclerosis. DNA was isolated from whole blood by Miller's method, and two polymorphisms were determined by PCR-RFLP procedure. The analysis of pon1 gene polymorphisms in patients with chronic renal failure showed following frequencies: 63 % QQ, 33 % QR, and 4 % RR for Q192R genotype ; 46 % LL, 46% LM, and 8 % MM for L55M genotype. In the control group we found rather similar frequencies: 60 % QQ, 34 % QR, 6 % RR for Q192R genotype, and 44 % LL, 43 % LM, and 13 % MM for L55M genotype. We also measured PON1 enzyme activity. Paraoxon was used as a substrate for measuring basal paraoxonase activity. PON1 enzyme activities significantly differed between two examined groups, median was 58, 00 (44, 00 to 144, 75) U/l for patients and 101, 00 (70, 00 to 231, 00 ) U/l for healthy volunteers (p< 0, 001). Based on our results we concluded that no significant differences concerning pon1 gene polymorphisms were found between patients with chronic renal failure and healthy volunteers (Q192R, p=0.64 ; and L55M, p=0.41). However, we found significantly lower enzyme activity in the patients. The lower PON1 activity in may indicate an increased risk of developing atherosclerosis and might be related to environmental factor (diet, lifestyle, drugs and disease) and/or other polymorphisms within pon1 gene.

Q192R; L55M; Paraoxonase; Polymorphisms

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