engleski

Paraoksonaze 1 polymorphisms and enzyme activity in hemodialysed patients

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. The aim was to determine the frequency of Q192R, L55M and -108C>T polymorphisms and PON1 activity in hemodialysed patients (N=263), and in the control group (N=238). Polymorphisms were determined by PCR-RFLP procedure and PON1 activity was assayed with paraoxon as a substrate in a presence of NaCl. No significant differences were found concerning Q192R and -108C>T polymorphisms between the two groups (p=0.339 and p=0.889, respectively). However, we have found different distribution of L55M genotypes (p=0.048). The observed frequencies were 44% LL, 48% LM and 8% MM in patient group and 45% LL, 41% LM and 14% MM in healthy controls. However, PON1 activities were significantly reduced in patient group [166 (106 to 366) U/l] as compared to healthy volunteers [228 (155 to 563) U/l]. In both groups genotypes RR, LL and CC were associated with the highest PON1 activity, as well as the haplotype combination RR LL CC. On the other hand, haplotype combination QQ MM TT was associated with the lowest PON1 activity. Observed variations in frequencies of L55M polymorphism do not explain a reduction in PON1 activity suggesting that lower activity might be related to environmental factors (diet, lifestyle, drugs and diseases) and/or other polymorphisms within pon1 gene.

paraoxonase 1; polymorphisms; enzyme activity

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