title: DPP4 gene DNA methylation in the omentum is associated with its gene expression and plasma lipid profile in severe obesity.
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 (%Meth(94-102)) was different between genotypes for DPP4 polymorphisms rs13015258 (P = 0.001), rs17848915 (P = 0.0004), and c.1926 G>A (P = 0.001). The %Meth(94-102) 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.
authors.affiliation: Nutraceuticals and Functional Foods Institute, Quebec, Quebec, Canada.
authors.forename: Valérie
authors.initials: V
authors.lastname: Turcot
authors.forename: Luigi
authors.initials: L
authors.lastname: Bouchard
authors.forename: Geneviève
authors.initials: G
authors.lastname: Faucher
authors.forename: André
authors.initials: A
authors.lastname: Tchernof
authors.forename: Yves
authors.initials: Y
authors.lastname: Deshaies
authors.forename: Louis
authors.initials: L
authors.lastname: Pérusse
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bélisle
authors.forename: Simon
authors.initials: S
authors.lastname: Marceau
authors.forename: Simon
authors.initials: S
authors.lastname: Biron
authors.forename: Odette
authors.initials: O
authors.lastname: Lescelleur
authors.forename: Laurent
authors.initials: L
authors.lastname: Biertho
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Vohl
mesh_terms: D000328:Adult; D015904:Biliopancreatic Diversion; D019175:DNA Methylation; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D050152:Intra-Abdominal Fat / Q000201:enzymology / Q000378:metabolism*; D008055:Lipids / Q000097:blood; D024821:Metabolic Syndrome / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D009767:Obesity, Morbid / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D009852:Omentum / Q000378:metabolism*; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D008055:Lipids; D012333:RNA, Messenger; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4