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Treatment with VPA has been shown to upregulate<jats:italic>Wfs1<\/jats:italic>expression<jats:italic>in vitro<\/jats:italic>. Aim of the present study was to compare the effect of chronic VPA treatment in wild type (WT) and<jats:italic>Wfs1<\/jats:italic>knockout (KO) mice on hepatic gene expression profile. Wild type,<jats:italic>Wfs1<\/jats:italic>heterozygous, and homozygous mice were treated with VPA for three months (300\u2009mg\/kg i.p. daily) and gene expression profiles in liver were evaluated using Affymetrix Mouse GeneChip 1.0\u2009ST array. We identified 42 genes affected by<jats:italic>Wfs1<\/jats:italic>genotype, 10 genes regulated by VPA treatment, and 9 genes whose regulation by VPA was dependent on genotype. Among the genes that were regulated differentially by VPA depending on genotype was peroxisome proliferator-activated receptor delta (<jats:italic>Ppard<\/jats:italic>), whose expression was upregulated in response to VPA treatment in WT, but not in<jats:italic>Wfs1<\/jats:italic>KO mice. 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