Paraoxonase-1 Serum Concentration and PON1 Gene Polymorphisms: Relationship with Non-Alcoholic Fatty Liver Disease

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is an important cause of chronic liver diseases around the world. Paraoxonase-1 (PON1) is an enzyme produced by the liver with an important antioxidant role. The aim of this study was to evaluate PON1 serum concentration and PON1 gene polymorphisms in patients with NAFLD. Materials and methods: We studied a group of 81 patients with NAFLD with persistently elevated aminotransferases and a control group of 81 patients without liver diseases. We collected clinical information and performed routine blood tests. We also measured the serum concentration of PON1 and evaluated the PON1 gene polymorphisms L55M, Q192R, and C-108T. Results: There was a significant difference (p < 0.001) in serum PON1 concentrations among the two groups. The heterozygous and the mutated homozygous variants (LM + MM) of the L55M polymorphism were more frequent in the NAFLD group (p < 0.001). These genotypes were found in a multivariate binary logistic regression to be independently linked to NAFLD (Odds ratio = 3.4; p = 0.04). In a multivariate linear regression model, the presence of NAFLD was associated with low PON1 concentration (p < 0.001). Conclusions: PON1 serum concentrations were diminished in patients with NAFLD, and the presence of NAFLD was linked with low PON1 concentration. The LM + MM genotypes of the PON1 L55M polymorphism were an independent predictor for NAFLD with persistently elevated aminotransferases. Author Contributions: Conceptualization, M.V.M., L.C., I.C.B. and M.A.; methodology, M.V.M., L.C., M.A., and S , .C.V.; validation, M.A., L.C., D.M.M., V.N., D.S. and S.P.; formal analysis, S , .C.V.; investigation, M.V.M., L.C., R.M.P., I.C.B. and S.P.; resources, I.C.B., S , .C.V., R.M.P., D.M.M., A.D.B. and A.L.R.; writing-original draft preparation, M.V.M.; writing-review and editing, S , .C.V., L.C., I.C.B. and M.A.; visualization, A.L.R.; supervision,

Pleiotropic Effects of Statins in the Light of Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis

“…Therefore decreasing PON1 and increased MDA might be a biochemical marker for lipid peroxidation which could be improved with statins resulting in the prevention of steatohepatitis. Moreover, LM + MM genotypes of the PON1 gene L55M polymorphism were found to be an independent predictor for the presence of NAFLD [22]. So the study proved the link of low PON1 concentrations and LM+MM genotypes of PON1 gene L55M polymorphism with NAFLD while statins improved it.…”

“…NASH or steatohepatitis progression depends on different factors such as FFA, inflammatory cytokines and adipokines, oxidative stress, and mitochondrial dysfunction [3]. FFA after beta and omega-oxidation accumulates reactive oxygen species (ROS) [22]. Proinflammatory cytokines including tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), which are produced by the liver and adipose tissue from nuclear factor kappa B (NF-κB) activation, are usually elevated and also associated with IR.…”

“…All were within the last seven years. Most of these were animal studies except the one by Milaciu et al [22], which is a human study but had several limitations such as not using liver biopsy to establish NAFLD diagnosis as the rest of the studies did, hence need to be proved by larger clinical trials on humans.…”

Bariatric surgery decreases oxidative stress and protein glycosylation in patients with morbid obesity

“…Some authors have concluded that the principal biochemical mechanisms involved in inducing OS in obesity are hyperleptinaemia, low antioxidant defences and chronic inflammation 28‐31 . Therefore, obesity is not only characterized by an OS state, but it is also defined as a low‐grade inflammatory disease.…”

“…Some authors have concluded that the principal biochemical mechanisms involved in inducing OS in obesity are hyperleptinaemia, low antioxidant defences and chronic inflammation. [28][29][30][31] Therefore, obesity is not only characterized by an OS state, but it is also defined as a low-grade inflammatory disease. In agreement with this, together with the low values of the antioxidant enzymes PON1 and CAT, we found leptin values 4 times higher in morbidly obese patients than 1 year after BS, in addition to high CRP levels that were 5 times higher before BS.…”