TNF-alpha promoter methylation in peripheral white blood cells: Relationship with circulating TNFoc, truncal fat and n-6 PUFA intake in young women

The aim of this article is to assess the potential relationships between TNF alpha gene promoter methylation in peripheral white blood cells and central adiposity (truncal fat), metabolic features and dietary fat intake. A group of 40 normal-weight young women (21 +/- 3 y; BMI 21.0 +/- 1.7 kg/m(2)) was included in this cross-sectional study. Anthropometric, biochemical and dietary data were assessed using validated procedures. DNA from white blood cells was isolated and 5-methylcytosine levels of the CpGs sites present in TNF alpha gene promoter (from 170 to +359 pb) were analyzed by Sequenom EpiTyper. Those women with high truncal fat ( >= 52.3%) showed lower 5-methylcytosine levels (P < 0.05) in the site CpG13 (at position +207) and CpG19 (+317 pb) of the TNF alpha gene promoter when were compared to women with lower truncal adiposity. The methylation levels of CpG13 were also correlated with circulating TNF alpha levels, which were higher in those women with greater truncal adiposity. In a linear regression model, truncal fat, HDL-cholesterol, insulin, plasma TNF alpha, and daily n-6 PUPA intake explained the methylation levels of CpG13 site +207 by 48% and the average of CpG13 and CpG19 by 43% (P < 0.001). In conclusion, women with higher truncal fat showed lower methylation levels of TNF alpha promoter in peripheral white blood cells and higher plasma TNF alpha concentrations. DNA methylation levels of TNF alpha promoter were associated with some metabolic features and with n-6 PUFA intake, suggesting a complex nutriepigenomic network in the regulation of this recognized pro-inflammatory marker. (C) 2013 Elsevier Ltd. All rights reserved.