Abstract

BackgroundGenetics explains a small proportion of variance in body mass index at the population level. Epigenetics, commonly measured by gene methylation, holds promise for understanding obesity risk factors and mechanisms.MethodsParticipants were 431 adolescents aged 10–15 years. BMI z-score, waist circumference z-score, and percent body fat were measured. Saliva samples were collected and methylation of promoter regions of four candidate genes or sequences (LEP, ICAM-1, CRH, and LINE-1) were measured in 3–4 CpG sites each. Linear regression was used to identify associations of methylation with obesity-related outcomes.ResultsAfter adjusting for age, in sex-stratified analysis, the three obesity-related outcomes were negatively associated with LEP methylation in obese boys only. There were no associations of methylation of the other genes or sequences and the obesity-related outcomes.ConclusionsOur results are consistent with prior studies that reported sex differences in associations of obesity-related outcomes with LEP methylation, and also as would be expected in adipose tissue, the source of circulating leptin. The findings suggest that saliva might be an acceptable tissue for epigenetics studies in adolescents.

Highlights

  • Genetics explains a small proportion of variance in body mass index at the population level

  • Methylation levels at all CpG sites measured in the CRH and ICAM-1 genes were low in both boys and girls with minimal variation

  • Mean methylation levels in LINE-1 were high for both boys and girls, and there were no differences by sex or obesity status

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Summary

Introduction

Genetics explains a small proportion of variance in body mass index at the population level. Epigenetics, commonly measured by gene methylation, holds promise for understanding obesity risk factors and mechanisms. Obese children and adolescents may experience physical and psychological consequences, such as increased risk for the development of diabetes and cardiovascular diseases as well as low self-esteem [2]. Childhood obesity often persists into adulthood [3], with associated increased risk of premature mortality [4]. In the USA, the prevalence of obesity in 2013–2014 for children and adolescents between 6–11 and 12–19 years. Epigenetic changes in genes related to stress and appetite have been studied as predictors of satiety, appetite, and obesity [11]. DNA methylation is the most frequent epigenetic mechanism studied. Dunstan et al Clinical Epigenetics (2017) 9:29 because it can be measured in surrogate tissues in large populations in quantitative assays. DNA methylation occurs primarily at cytosine within cytosine-guanine dinucleotides (CpG), and it affects gene expression by modifying the degree to which the DNA is accessible to promoters or suppressors [12]

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