Association between variants of PNPLA3 (rs738409), UCP2 (rs660339) and HFE (rs1800562, rs1800730, rs1799945) genes and changes in the functioning of the lipid peroxidation – antioxidant defense system in plasma in non-alcoholic fatty liver disease patients

Currently reaching epidemic proportions, non-alcoholic fatty liver disease (NAFLD) particularly affects individuals of employable age. The pathogenesis of NAFLD involves a combination of hereditary factors and external influences that collectively disrupt lipid and carbohydrate metabolic pathways and impair the balance between lipid peroxidation and antioxidant protection mechanisms. To date, there has been limited exploration of the possible relationship between these pathological changes and specific variants of the PNPLA3, UCP2, and HFE genes.
The aim. To examine the association between some markers of the LPO-AOD system in plasma depending on polymorphic variants of the PNPLA3, UCP2 and HFE genes.
Materials and methods. For this study, we collected whole blood samples from 116 patients with NAFLD (65 with steatosis and 51 with steatohepatitis) and 100 healthy volunteers. All participants had peripheral venous blood collected for subsequent molecular genetic and biochemical analysis.
Results. Our findings indicate that in steatosis, catalase activity was elevated in carriers of the rs660339 TT genotype, while SOD activity was reduced in those with the rs738409 GG variant.
For steatohepatitis patients, ceruloplasmin levels were altered in opposite directions based on genotype: the rs1800730 TT variant was associated with lower levels, whereas the rs660339 TT genotype was linked to higher levels.
Conclusions. Polymorphisms rs738409 of the PNPLA3 gene, rs1800730 of the HFE gene and rs660339 of the UCP2 gene are associated with an imbalance in the LPOAOD system, which may be caused by an increase of the iron level and a change in the antioxidant activity of the UCP2 protein, as well as an increase in the production of prooxidants.

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