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RESEARCH PRODUCT

Short-Term Effects on Gene-Expression and on DNA-Methylation at the Genome-Wide Level of the Iberian Ham Intake and Compared With Orange Intake: A Crossover Randomized Trial

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OBJECTIVES: Diet regulates gene expression and methylation profiles by several mechanisms. However, studies analyzing the simultaneous effect of specific foods on gene-expression and DNA methylation at the genome-wide level are very scarce. Therefore our aims were: To study the short-term transcriptomics and epigenomcis effects at the genome-wide level of the Iberian ham intake compared with orange intake in the same subjects. METHODS: We carried out a cross-over randomized trial (registered at ISRCTN17906849) in 33 healhty volunteers (aged 18–50 years and 50% females) of European ancestry. After 12h fasting, participants were randomly allocated to eat 67.5 g of Iberian ham (100% pure iberian breed and 100% acorn fed) or 500 g of peeled oranges (Citrus reticulata) depening on the intervention group. After a washout period, subjects were crossed over to the alternate treatment arm. Blood samples were taken at 0-h and at 4-h to isolate DNA and RNA from leukocytes. A random sample of 16 participants was selected for omics analyses (gene expression with the. GeneChip Human Gene 2.0 ST Array, and the EPIC-Illumina array (850K) for methylation). Eight arrays (2 times and 2 treatments per 2 omics) were obtained for each participant. Differences in gene expression and methylation (4 h vs baseline) were analyzed for Iberian ham, oranges and combined. Kyoto Encyclopedia of Genes and Genomes (KEGG) was used for pathway enrichment analysis. RESULTS: The top-ranked genes differentially expressed P < 1 × 10(–5)) after Iberian ham intake (4 h vs baseline) were PKBP5 and PICALM. Pantothenate and CoA biosyntesis and the JAK-STAT singaling pathways were the most significantly enriched (P < 5 × 10(–7)). After orange intake, the top-ranked differentially expressed genes (P < 5 × 10(–6)) were: SMAP2 and RHEB, the pathways being (P < 5 × 10(–9)): Cellular senescence and ABC transporters. We detected top-ranked methylated CpGs both for ham and oranges, resulting the Chemokine signaling pathway differentially methylated for oranges and in the Neurothrophine singaling pathway for Iberian ham intake. Comparative combined analysis revealed additional differences. CONCLUSIONS: A short-term intake of Iberian ham or oranges results in differences in gene expression as well as in DNA-methylation. FUNDING SOURCES: CIBEROBN-06/03/035, PROMETEO-17/2017 APOSTD/2019/136), P1–1B2013–54 and COGRUP/2016/06