Comparison of the dipeptidyl peptidase-4 gene methylation levels between severely obese subjects with and without the metabolic syndrome

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.