Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8343572 | Molecular Genetics and Metabolism | 2018 | 40 Pages |
Abstract
A sustained activation of the unfolded protein response and the subsequent endoplasmic reticulum (ER) stress has been involved in the onset and severity of several metabolic diseases. The aim of this study was to analyze the association of DNA methylation signatures at ER stress genes with adiposity traits and related metabolic disorders. An epigenomic analysis within the Methyl Epigenome Network Association (MENA) project was conducted in an adult population (n = 474). DNA methylation status in peripheral white blood cells was analyzed by a microarray approach. KEGG database was used to the characterization and discrimination of genes involved in the “protein processing in endoplasmic reticulum pathway”. Anthropometric measurements and plasma metabolic profiles were analyzed. A total of 15 CpG sites at genes participating in ER pathway were strongly correlated with BMI after adjusted linear regression analyses (p < 0.0001). These included cg08188400 (MAP2K7), cg20541779 (CASP12), cg24776411 (EIF2AK1), cg14190817 (HSPA5), cg21376454 (ERN1), cg06666486 (EIF2AK1), cg03211481 (DNAJC1), cg18357645 (OS9), cg05801879 (MBTPS1), cg20964082 (ERO1LB), cg17300868 (NFE2L2), cg03384128 (EIF2AK4), cg02712587 (EIF2AK4), cg04972384 (SELS), cg02240686 (EIF2AK2). Noteworthy, most of them were implicated in ER stress (p = 2.9E â 09). However, only methylation levels at cg20964082 (ERO1LB), cg17300868 (NFE2L2), cg05801879 (MBTPS1), and cg03384128 (EIF2AK4) also correlated with total fat mass. Interestingly, significant associations between methylation patterns at cg20964082 (ERO1LB) and cg17300868 (NFE2L2) and insulin and HOMA-IR index were found, whereas cg05801879 (MBTPS1) and cg03384128 (EIF2AK4) were correlated with triglyceride levels. This study suggests associations of methylation signatures at ER stress genes with adiposity and insulin resistance, as revealed by discriminative pathway analyses.
Keywords
SREBPsLDL-CCpGEIF2AK2HDL-CUPReIF2αS1PDXASKI-1VLDL-CMENAmitogen-activated protein kinase kinase 7NFE2L2Selenoprotein SSREBP-1aDiogenesGCN2EIF2AK4HSPA5MBTPS1SREBP-1PPARγ2SREBP-2SPSSFDRSBPFASLIMMANrf2SREBP-1cDBPTyGHOMA-IRfatty acid synthaseEpigeneticsStatistical Package for the Social SciencesTriglyceridesdual-energy X-ray absorptiometryKEGG یا Kyoto Encyclopedia of Genes and Genomes Kyoto Encyclopedia of Genes and GenomesWaist circumferenceRegressionSite-1 proteaseICTUSbody mass indexBMIendoplasmic reticulumdiastolic blood pressuresystolic blood pressurehigh-density lipoprotein cholesterolObesityInsulin resistancefalse discovery rateSelSUnfolded protein responsesterol regulatory element binding protein 2Sterol regulatory element binding protein 1Sterol regulatory element binding protein 1cPREDIMEDCaspase 12total cholesterolVery low-density lipoprotein cholesterolLow-density lipoprotein cholesterol
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Authors
Omar Ramos-Lopez, Jose I. Riezu-Boj, Fermin I. Milagro, J. Alfredo Martinez, on behalf of the MENA Project on behalf of the MENA Project,