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Alterations in Lipidome Profiles Distinguish Early-Onset Hyperuricemia, Gout, and the Effect of Urate-Lowering Treatment

ABSTRACT: Objective: Our study aimed to evaluate differences in plasma lipidome between patients with asymptomatic hyperuricemia (HUA) detected < 40 years (HUA<40) and > 40 years, gout patients with disease onset < 40 years (Gout<40) and > 40 years, and normouricemic healthy controls. Methods: Plasma samples were collected from 94 asymptomatic HUA (77% HUA<40) subjects, 196 gout patients (59% Gout<40), and 70 normouricemic controls. A comprehensive targeted lipidomic analysis was performed to semi-quantify 608 lipids in plasma. Univariate and multivariate statistics and advanced visualizations were applied. Results: Both HUA and gout patients showed similar changes in lipid profiles with the highest upregulation of phosphatidylethanolamines (median fold-changes and p-values were 2.9/3.4 and p=1.5x10-16/p=5.5x10-21 for HUA/Gout, respectively) and downregulation of lysophosphatidylcholine plasmalogens/plasmanyls (median fold-changes and p-values were 0.3/0.5 and p=4.8x10-21/p=2.2x10-21 for HUA/Gout, respectively). More profound changes were observed in HUA<40 and Gout<40. Moreover, a shift in the lipid profile towards controls was apparent in HUA<40 and Gout<40 during urate-lowering treatment. Multivariate statistics differentiated HUA<40 and Gout<40 groups from controls with an overall accuracy of > 94%. Conclusion: The changes in the lipidome of HUA and Gout patients show a significant impact on lipid metabolism and a severe pathobiochemical effect, with no relationship with common determinants such as body mass index, metabolic syndrome, or pathogenic variants in major urate transporter ABCG2. The most significant glycerophospholipid dysregulation was found in HUA<40 and Gout<40 patients, together with a correction of this imbalance with urate-lowering treatment.

INSTRUMENT(S): QTRAP 6500+

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Blanka Stiburkova

PROVIDER: MSV000091596 | MassIVE | Thu Mar 30 13:11:00 BST 2023

REPOSITORIES: MassIVE

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Alterations in Lipidome Profiles Distinguish Early-Onset Hyperuricemia, Gout, and the Effect of Urate-Lowering Treatment

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