title: Comparison of the dipeptidyl peptidase-4 gene methylation levels between severely obese subjects with and without the metabolic syndrome.
abstract: BACKGROUND
  The dipeptidyl peptidase-4 (DPP4) enzyme is a novel adipokine potentially involved in the development of the metabolic syndrome (MetS). Previous observations demonstrated higher visceral adipose tissue (VAT) DPP4 gene expression in non-diabetic severely obese men with (MetS+) vs. without (MetS-) MetS. DPP4 mRNA abundance in VAT correlated also with CpG site methylation levels (%Meth) localized within and near its exon 2 (CpG94 to CpG102) in non-diabetic severely obese women, regardless of their MetS status. The actual study tested whether DPP4 %Meth levels in VAT are different between MetS- and MetS+ non-diabetic severely obese subjects, whether variable metabolic and plasma lipid profiles are observed between DPP4 %Meth quartiles, and whether correlation exists in DPP4 %Meth levels between VAT and white blood cells (WBCs).
  
  
  METHODS
  DNA was extracted from the VAT of 26 men (MetS-: n=12, MetS+: n=14) and 79 women (MetS-: n=60; MetS+: n=19), as well as from WBCs in a sub-sample of 17 women (MetS-: n=9; MetS+: n=8). The %Meth levels of CpG94 to CpG102 were assessed by pyrosequencing of sodium bisulfite-treated DNA. ANOVA analyses were used to compare the %Meth of CpGs between MetS- and MetS+ groups, and to compare the metabolic phenotype and plasma lipid levels between methylation quartiles. Pearson correlation coefficient analyses were computed to test the relationship between VAT and WBCs CpG94-102 %Meth levels.
  
  
  RESULTS
  No difference was observed in CpG94-102 %Meth levels between MetS- and MetS+ subjects in VAT (P=0.67), but individuals categorized into CpG94-102 %Meth quartiles had variable plasma total-cholesterol concentrations (P=0.04). The %Meth levels of four CpGs in VAT were significantly correlated with those observed in WBCs (r=0.55-0.59, P≤0.03).
  
  
  CONCLUSIONS
  This study demonstrated that %Meth of CpGs localized within and near the exon 2 of the DPP4 gene in VAT are not associated with MetS status. The actual study also revealed an association between the %Meth of this locus with plasma total-cholesterol in severe obesity, which suggests a link between the DPP4 gene and plasma lipid levels.
authors: Institute of Nutraceuticals and Functional Foods (INAF), Pavillon des Services, Université Laval, 2440 Hochelaga Blvd, G1V 0A6, Québec, Canada. marie-claude.vohl@fsaa.ulaval.ca.
authors: Valérie
authors: V
authors: Turcot
authors: André
authors: A
authors: Tchernof
authors: Yves
authors: Y
authors: Deshaies
authors: Louis
authors: L
authors: Pérusse
authors: Alexandre
authors: A
authors: Bélisle
authors: Picard
authors: P
authors: Marceau
authors: Frédéric-Simon
authors: FS
authors: Hould
authors: Stéfane
authors: S
authors: Lebel
authors: Marie-Claude
authors: MC
authors: Vohl
references: Nat Med. 2011 May;17(5):610-7
references: 21499269
references: Diabetes. 2011 Jul;60(7):1917-25
references: 21593202
references: Cancer Immunol Immunother. 2009 Nov;58(11):1723-47
references: 19557413
references: Nat Genet. 2009 Feb;41(2):178-186
references: 19151715
references: J Neurosci. 2008 Dec 31;28(53):14428-34
references: 19118176
references: Int J Obes (Lond). 2009 Sep;33(9):978-90
references: 19564875
references: Clin Biochem. 2013 Mar;46(4-5):300-3
references: 23219738
references: Diabetes Care. 2003 Jan;26 Suppl 1:S5-20
references: 12502614
references: Genome Res. 2008 Sep;18(9):1518-29
references: 18577705
references: Diabet Med. 2006 May;23(5):469-80
references: 16681555
references: J Mol Med (Berl). 2002 Dec;80(12):753-69
references: 12483461
references: Clin Pharmacol Ther. 2010 Apr;87(4):407-16
references: 20200516
references: Obes Surg. 2007 Mar;17(3):372-82
references: 17546847
references: Appl Physiol Nutr Metab. 2007 Feb;32(1):89-114
references: 17332787
references: Diabetologia. 2006 Sep;49(9):2049-57
references: 16816950
references: Nat Rev Genet. 2011 Jul 12;12(8):529-41
references: 21747404
references: Immunogenetics. 1994;40(5):331-8
references: 7927537
references: Mol Genet Metab. 2005 Sep-Oct;86(1-2):300-6
references: 16122961
references: Obesity (Silver Spring). 2011 Feb;19(2):388-95
references: 20847730
references: Hum Genet. 2012 Jan;131(1):57-66
references: 21701784
references: Mol Cell Proteomics. 2012 Jul;11(7):M111.016915
references: 22398368
references: Acta Diabetol. 2009 Mar;46(1):13-21
references: 18682883
references: Obes Res. 2004 Aug;12(8):1217-22
references: 15340102
references: Life Sci. 2000;66(2):91-103
references: 10666005
references: J Nutr. 1995 Feb;125(2):183-8
references: 7861244
references: World J Surg. 1998 Sep;22(9):947-54
references: 9717420
references: Immunology. 1997 May;91(1):151-8
references: 9203979
references: JAMA. 2001 May 16;285(19):2486-97
references: 11368702
references: Nat Med. 2009 Aug;15(8):921-9
references: 19633657
references: Immunology. 1993 Nov;80(3):465-70
references: 7904591
references: Int J Hematol. 2004 Oct;80(3):254-60
references: 15540901
references: Front Biosci. 2008 Jan 01;13:2435-43
references: 17981724
references: Crit Rev Clin Lab Sci. 2003 Jun;40(3):209-94
references: 12892317
references: Nutr Metab Cardiovasc Dis. 2010 May;20(4):224-35
references: 19515542
references: Nat Med. 1998 Dec;4(12):1434-7
references: 9846584