DPP4 Gene DNA Methylation in the Omentum is Associated With Its Gene Expression and Plasma Lipid Profile in Severe Obesity |
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| Authors: | Valérie Turcot Luigi Bouchard Geneviève Faucher André Tchernof Yves Deshaies Louis Pérusse Alexandre Bélisle Simon Marceau Simon Biron Odette Lescelleur Laurent Biertho Marie‐Claude Vohl |
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| Institution: | 1. Nutraceuticals and Functional Foods Institute, Quebec, Quebec, Canada;2. Molecular Endocrinology and Genomics, CHUL, Laval University, Quebec, Quebec, Canada;3. University of Montreal Community Genomics Medicine Centre, Chicoutimi Hospital, Chicoutimi, Canada;4. Quebec Heart and Lung Institute, Faculty of Medicine, Laval University, Quebec, Quebec, Canada;5. Department of Preventive Medicine, Laval University, Quebec, Quebec, Canada;6. Genotyping Platform Team, McGill University and Genome Quebec Innovation Center, Montreal, Quebec, Canada |
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| Abstract: | Severely obese subjects with the metabolic syndrome (MS) have higher dipeptidyl peptidase‐4 (DPP4) expression in their visceral adipose tissue (VAT) compared to obese individuals without MS. We tested the hypothesis that methylation level of CpG sites in the DPP4 promoter CpG island in VAT was genotype‐dependent and associated with DPP4 mRNA abundance and MS‐related phenotypes. The VAT DNA was extracted in 92 severely obese premenopausal women undergoing biliopancreatic derivation for the treatment of obesity. Women were nondiabetic and none of them used medication to treat MS features. Cytosine methylation rates (%) of 102 CpG sites in the DPP4 CpG island were assessed by pyrosequencing of sodium bisulfite‐treated DNA. Methylation rates were >10% for CpG sites 94–102. Their mean methylation rate (%Meth94–102) was different between genotypes for DPP4 polymorphisms rs13015258 (P = 0.001), rs17848915 (P = 0.0004), and c.1926 G>A (P = 0.001). The %Meth94–102 correlated negatively with DPP4 mRNA abundance (r = ?0.25, P < 0.05) and positively with plasma high‐density lipoprotein (HDL) cholesterol concentrations (r = 0.22, P < 0.05), whereas DPP4 mRNA abundance correlated positively with plasma total‐/HDL‐cholesterol ratio (r = 0.25; P < 0.05). In the VAT of nondiabetic severely obese women, genotype‐dependent methylation levels of specific CpG sites in the DPP4 promoter CpG island were associated with DPP4 gene expression and variability in the plasma lipid profile. Higher DPP4 gene expression in VAT and its relationship with the plasma lipid profile may be explained by actually unknown DPP4 biological effect or, to another extent, may also be a marker of VAT inflammation known to be associated with metabolic disturbances. |
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