LINE-1 methylation in visceral adipose tissue of severely obese individuals is associated with metabolic syndrome status and related phenotypes
1 Institute of Nutraceuticals and Functional Foods, 2440 Hochelaga Blvd, Québec City, G1V 0A6, Canada
2 Molecular Endocrinology and Genomics, CHUL Research Center, 2705 Laurier Blvd, Québec City, G1V 4G2, Canada
3 Department of Food Sciences and Nutrition, Université Laval, 2425 de l’Agriculture Av, Québec City, G1V 0A6, Canada
4 Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, 2725 Sainte-Foy Rd, Québec City, G1V 4G5, Canada
5 Department of Medicine, Université Laval, 1050 de la Médecine Av, Québec City, G1V 0A6, Canada
6 Department of Kinesiology, Université Laval, 2300 de la Terrasse Street, Québec City, G1V 0A6, Canada
7 Genotyping Platform Team, McGill University and Génome Québec Innovation Center, 740 Docteur-Penfield Av, Montréal, H3A 1A4, Canada
8 Department of Surgery, Université Laval, 1050 de la Médecine Av, Québec City, G1V 0A6, Canada
Clinical Epigenetics 2012, 4:10 doi:10.1186/1868-7083-4-10Published: 2 July 2012
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.
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.
DNA was extracted from VAT of 34 men (MetS-: n = 14, MetS+: n = 20) and 152 premenopausal women (MetS-: n = 84; MetS+: n = 68) undergoing biliopancreatic diversion for the treatment of obesity. LINE-1%meth levels were assessed by pyrosequencing of sodium bisulfite-treated DNA.
The mean LINE-1%meth in VAT was of 75.8% (SD = 3.0%). Multiple linear regression analyses revealed that LINE-1%meth was negatively associated with fasting glucose levels (β = -0.04; P = 0.03), diastolic blood pressure (β = -0.65; P = 0.03) and MetS status (β = -0.04; P = 0.004) 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) = 4.37, P = 0.004) and the second (Q2: OR = 4.76, P = 0.002) quartiles compared to Q4 (1.00) when adjusting for age, sex and smoking.
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.