Oxylipin Profiles in Plasma of Patients with Wilson's Disease.

Nadezhda V Azbukina,Alina A Astakhova,Tatiana N Fedorova,Vsevolod V Poleshuk,Rogneda B Kazanskaya,Dmitry V Chistyakov,Alexander V Lopachev,Marina G Sergeeva,Sergei V Goriainov

doi:10.3390/metabo10060222

Abstract

Wilson’s disease (WD) is a rare autosomal recessive metabolic disorder resulting from mutations in the copper-transporting, P-type ATPase gene ATP7B gene, but influences of epigenetics, environment, age, and sex-related factors on the WD phenotype complicate diagnosis and clinical manifestations. Oxylipins, derivatives of omega-3, and omega-6 polyunsaturated fatty acids (PUFAs) are signaling mediators that are deeply involved in innate immunity responses; the regulation of inflammatory responses, including acute and chronic inflammation; and other disturbances related to any system diseases. Therefore, oxylipin profile tests are attractive for the diagnosis of WD. With UPLC-MS/MS lipidomics analysis, we detected 43 oxylipins in the plasma profiles of 39 patients with various clinical manifestations of WD compared with 16 healthy controls (HCs). Analyzing the similarity matrix of oxylipin profiles allowed us to cluster patients into three groups. Analysis of the data by VolcanoPlot and partial least square discriminant analysis (PLS-DA) showed that eight oxylipins and lipids stand for the variance between WD and HCs: eicosapentaenoic acid EPA, oleoylethanolamide OEA, octadecadienoic acids 9-HODE, 9-KODE, 12-hydroxyheptadecatrenoic acid 12-HHT, prostaglandins PGD2, PGE2, and 14,15-dihydroxyeicosatrienoic acids 14,15-DHET. The compounds indicate the involvement of oxidative stress damage, inflammatory processes, and peroxisome proliferator-activated receptor (PPAR) signaling pathways in this disease. The data reveal novel possible therapeutic targets and intervention strategies for treating WD.

Highlights

Wilson’s disease (WD) is a rare autosomal recessive metabolic disorder resulting from mutations in the copper-transporting, P-type ATPase gene, ATP7B gene, which encodes a copper-transportingP-type ATPase [1]
Besides different ATP7B mutations [8], other genetic variations may influence the variability in WD manifestation, such as apolipoprotein E (APOE), human prion protein (PRNP), 5,10-methylenetetrahydrofolate reductase (MTHFR), the interleukin-1 receptor antagonist (IL1RN), peroxisomal catalase, and other genes [7,9]
Derivatives of omega-3, and omega-6 polyunsaturated fatty acids (PUFAs) are signaling mediators that are deeply involved in innate immunity responses; the regulation of inflammatory responses, including acute and chronic inflammation; and other disturbances related to any system disease [14,15,16,17]

Summary

Introduction

Wilson’s disease (WD) is a rare autosomal recessive metabolic disorder resulting from mutations in the copper-transporting, P-type ATPase gene, ATP7B gene, which encodes a copper-transportingP-type ATPase [1]. Wilson’s disease (WD) is a rare autosomal recessive metabolic disorder resulting from mutations in the copper-transporting, P-type ATPase gene, ATP7B gene, which encodes a copper-transporting. The manifestations of WD are variable, and, in addition to liver diseases, may include neurological and/or psychiatric symptoms, as well as abnormalities in the blood or kidneys. It is hypothesized that other genetic and/or environmental factors could influence the phenotypes of WD [5,7]. Besides different ATP7B mutations [8], other genetic variations may influence the variability in WD manifestation, such as apolipoprotein E (APOE), human prion protein (PRNP), 5,10-methylenetetrahydrofolate reductase (MTHFR), the interleukin-1 receptor antagonist (IL1RN), peroxisomal catalase, and other genes [7,9]. The influence of epigenetics, environment, age, and sex-related factors on the WD phenotype further complicates diagnosis [3,7,10]

Methods

Discussion

Conclusion