engleski

POLYMORPHISMS OF PARAOXONASE 1 GENE AND CHRONIC RENAL FAILURE

Paraoxonase 1 (PON1), an HDL-associated enzyme, might play an important role in lipid metabolism and protect against development of atherosclerosis. Polymorphisms in coding (Q192R and L55M) and promoter (-108 C>T) regions of pon1 gene affect PON1 activity. Patients with chronic renal failure undergoing haemodialysis may have an increased risk of developing atherosclerosis and have reduced PON1 activity. We carried out this study in order to determine frequencies of Q192R, L55M and -108 C>T polymorphisms and PON1 activity in patients with chronic renal failure undergoing hemodialysis (N=71), and compared obtained results with the control group (N=88). DNA was isolated from whole blood by Miller's method, and three polymorphisms were determined by PCR-RFLP procedure. Paraoxonase activity was assayed with paraoxon as a substrate and in presence of NaCl. The analysis of pon1 gene polymorphisms in patients group showed following frequencies: 55 % QQ, 39 % QR, and 6 % RR for Q192R genotype ; 41 % LL, 53% LM, and 6 % MM for L55M genotype ; 21 % CC, 59 % CT, and 20 % TT for -108 C>T genotype. In the control group we found rather similar frequencies: 53 % QQ, 37 % QR, 10 % RR for Q192R genotype ; 46 % LL, 38 % LM, and 16 % MM for L55M genotype ; 25 % CC, 52 % CT, and 23 % TT for -108 C>T genotype. PON1 enzyme activities significantly differed between two examined groups, median was 159 (114 to 378) U/l for patients and 284 (178 to 589 ) U/l for healthy volunteers. No significant differences was found concerning Q192R and -108C>T polymorphisms between patients and healthy volunteers (Q192R, p=0.569 ; -108C>T, p=0.685). However, we have found significantly lower enzyme activity (p<0.001) and different distribution of L55M genotypes (p=0.045) in the patients group. M allele is associated with lower serum PON1 activity and observed differences in frequencies of L55M genotype might not explain a reduction in PON1 activity. The lower PON1 activity might be related to environmental factors (diet, lifestyle, drugs and diseases) and/or other polymorphisms within pon1 gene.

Paraoxonase1; Polymorphisms; Chronic renal failure

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