Paraoxonase1 (PON1) 55 and 192 Polymorphism in Egypt and its impact on the antioxidant status of patients with Bilharzial and Viral liver diseases

Background/Aims: It is now known beyond doubt that viral hepatitis (caused by B or
C virus) along with bilharzial infestation (mostly S. mansoni) are the most important
factors responsible for the vast majority of morbidity and mortality in Egypt. Based
upon the concept that oxidative stress plays a key role in the development and
pathogenesis of chronic liver diseases, many of the factors known to have antioxidant
properties are to be investigated for purpose of evaluating their role in the defense
mechanisms against all oxidant brunts associated with liver diseases. Serum MDA
was assayed as a famous marker of oxidative stress, while PON1 enzyme activities
were investigated as a marker of antioxidant properties. The polymorphism at 55 and
192 position known to be associated with PON1 enzyme are also investigated in
Egyptian normal and chronic liver patients, in order to elucidate whether such
polymorphism has any effect on the enzyme activity, and consequently the state of
hepatic affection. Whether routine assay of PON1 activity in chronic liver disease
patients can be introduced as a non-invasive clue marker for diagnosis and rating the
stage of hepatic affection is another aim of the present work. Methods: We studied 75
patients with chronic liver disease (25 patient with chronic Bilharziasis, 25 patients
with chronic hepatitis C, 25 patients with mixed hepatitis C and bilharzial cirrhosis)
and 25 apparently healthy controls. Serum paraoxonase activity and levels of the
lipid peroxidation marker (serum malondialdhyde) were measured
spectrophotomtrically. PON1 genotyping at positions 55 and 192 were analyzed by
PCR, restriction fragment length polymorphism and agarose gel electrophoresis.
Results: the present work showed that chronic liver disease (viral and/or bilharzial)
are associated with elevated oxidative stress (as indicated by increased MDA level)
together with reduced PON1-activities, which is regarded as an antioxidant tool. The
frequency of investigated polymorphism at 55 and 192 position were found to be of no
statistical significance between patients and control groups. The MDA and PON1
values did correlate with standard liver function. Conclusion: The present work
could introduce the assay of PON1 activity in the serum as a non-invasive, specific
and reliable marker in a trial to assess the state of liver affection in chronic hepatic
diseases.