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A genomics approach is an effective way to understand the possible mechanisms underlying the onset and progression of disease. However, very limited results have been published regarding whole-genome expression analysis of human idiopathic membranous nephropathy (iMN) using renal tissue. In the present study, gene expression profiling using renal cortex tissue from iMN patients and healthy controls was conducted; differentially expressed genes (DEGs) were filtered out, and 167 up- and 291 down-regulated genes were identified as overlapping DEGs (ODEGs). Moreover, enrichment analysis and protein-protein network construction were performed, revealing enrichment of genes mainly in cholesterol metabolism and arachidonic acid metabolism, among others, with 38 hub genes obtained. Furthermore, we found several associations between circulating lipid concentrations and hub gene signal intensities in the renal cortex. Our findings indicate that lipid metabolism, including cholesterol metabolism and arachidonic acid metabolism, may participate in iMN pathogenesis through key genes, including apolipoprotein A1 (APOA1), apolipoprotein B (APOB), apolipoprotein C3 (APOC3), cholesteryl ester transfer protein (CETP), and phospholipase A2 group XIIB (PLA2G12B). [ABSTRACT FROM AUTHOR]