Influence of lifestyle on the FAIM2 promoter methylation between obese and lean children: a cohort study

Objective: An obesity-related gene, Fas apoptotic inhibitory molecule 2 (FAIM2), is regulated by nutritional state and the methylation levels of the FAIM2 promoter are significantly associated with obesity. Lifestyle factors, such as sedentary behaviour and physical activity, might modify epigenetic patterns that have been related to obesity. Whether the molecular mechanisms by which FAIM2 affects obesity are involved in lifestyle is unclear. This study investigates the potential differences of the FAIM2 promoter methylation with sedentary behaviour and physical activity in obese and lean children. Design: Cohort study. Setting: Institute of Pediatrics in China. Participants: 59 obese cases and 39 lean controls aged 8-18 years recruited from a cross-sectional survey of children from Beijing in 2013. Primary and secondary outcome measures: The FAIM2 promoter methylation was quantified using the Sequenom MassARRAY platform. Sedentary behaviour and physical activity were investigated using a questionnaire. The influences of different lifestyles on methylation variations in obese and lean children were examined by multiple linear regression. Results: The methylation levels at seven CpG sites of the FAIM2 promoter were significantly associated with sedentary behaviour, especially the methylation levels at site -975, site -413, sites -362 and -360, and sites -353 and -349 (p=0.00004, 0.00009, 0.0006 and 0.00005, respectively). There were significant differences between the methylation levels at four CpG sites in obese and lean participants with high or moderate physical activity level <150 min/week. Conclusions: This study provides the first evidence that there are significant differences in the associations of the FAIM2 promoter methylation with sedentary behaviour and physical activity between obese and lean children. Our results suggest that lifestyle may possibly be mediating the process of the FAIM2 involved in obesity.