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

ABSTRACT

The aim of this article is to assess the potential relationships between TNFα 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 ± 3y; 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 TNFα 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 TNFα gene promoter when were compared to women with lower truncal adiposity. The methylation levels of CpG13 were also correlated with circulating TNFα levels, which were higher in those women with greater truncal adiposity. In a linear regression model, truncal fat, HDL-cholesterol, insulin, plasma TNFα, and daily n-6 PUFA 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 TNFα promoter in peripheral white blood cells and higher plasma TNFα concentrations. DNA methylation levels of TNFα 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.