文摘
Background Epigenetic mechanisms may be involved in the regulation of genes found to be differentially expressed in the visceral adipose tissue (VAT) of severely obese subjects with (MetS+) versus without (MetS-) metabolic syndrome (MetS). Long interspersed nuclear element 1 (LINE-1) elements DNA methylation levels (%meth) in blood, a marker of global DNA methylation, have recently been associated with fasting glucose, blood lipids, heart diseases and stroke. Aim To test whether LINE-1%meth levels in VAT are associated with MetS phenotypes and whether they can predict MetS risk in severely obese individuals. Methods DNA was extracted from VAT of 34 men (MetS-: n--4, MetS+: n--0) and 152 premenopausal women (MetS-: n--4; MetS+: n--8) undergoing biliopancreatic diversion for the treatment of obesity. LINE-1%meth levels were assessed by pyrosequencing of sodium bisulfite-treated DNA. Results The mean LINE-1%meth in VAT was of 75.8% (SD--.0%). Multiple linear regression analyses revealed that LINE-1%meth was negatively associated with fasting glucose levels (β--0.04; P--.03), diastolic blood pressure (β- -0.65; P--.03) and MetS status (β--0.04; P--.004) after adjustments for the effects of age, sex, waist circumference (except for MetS status) and smoking. While dividing subjects into quartiles based on their LINE-1%meth (Q1 to Q4: lower %meth to higher %meth levels), greater risk were observed in the first (Q1: odds ratio (OR)--.37, P--.004) and the second (Q2: OR--.76, P--.002) quartiles compared to Q4 (1.00) when adjusting for age, sex and smoking. Conclusions These results suggest that lower global DNA methylation, assessed by LINE-1 repetitive elements methylation analysis, would be associated with a greater risk for MetS in the presence of obesity.