Background: Periconceptional dietary changes have been associated with altered methylation at the H19/Insulin like growth factor (IGF)2 locus. Further H19/IGF2 DMR (differentially methylated region) methylation has been associated with obesity in this and other cohorts.
Objective: To investigate associations between H19 /IGF2 DMR methylation at 17 years and body fat distribution measured at 20 years.
Methods: Western Australian Pregnancy Cohort (Raine study) adolescents (age = 16.5±0.5 years) (n=207; 135 Male and 117 females) were included. H19/IGF2 DMR methylation was measured at 17 years and body composition was undertaken by Dual Energy X-Ray Absorptiometry (DEXA) at 20 years old. DNA methylation was measured at twelve cytosine-phosphate-guanine sites (CpGs), analysed as Sequenom MassARRAY EpiTYPER units within the IGF2/H19 ICR.
Statistical methods: Principle components analysis was undertaken on twelve H19/IGF2 CpGs. H19/IGF2 DNA methylation principle components were investigated for their association with body composition and anthropometry using linear regression analysis, adjusted for physical activity, healthy and western dietary patterns, kilojoule intake, sex and ethnicity.
Results: There were 135 males and 117 females participants. The first principal component of IGF2/H19 ICR DNA methylation (representing mean methylation across all CpG units) positively associated with fat mass in all regions of the body (total, central and peripheral distributions) (all p<0.05). It was not associated with anthropometry (BMI, waist or waist-hip circumference), soft tissue or lean mass.
Conclusions: H19/IGF2 DMR methylation is associated with body fat distributed both centrally and peripherally. This provides further evidence that DNA methylation of specific loci is associated with adiposity patterns. It also highlights the potential impact of the early environment on “programming” of a subsequent metabolically adverse body fat distribution.