Postnatal Growth and DNA Methylation Are Associated With Differential Gene Expression of the TACSTD2 Gene and Childhood Fat Mass

Rapid postnatal growth is associated with increased risk of childhood adiposity. The aim of this study was to establish whether this pathway is mediated by altered DNA methylation and gene expression. Two distinct cohorts, one preterm (n = 121) and one term born (n = 6,990), were studied. Exploratory analyses were performed using microarrays to identify differentially expressed genes in whole blood from children defined as slow (n = 10) compared with rapid (n = 10) postnatal (term to 12 weeks corrected age) growers. Methylation within the identified TACSTD2 gene was measured in both cohorts, and rs61779296 genotype was determined by Pyrosequencing or imputation and analyzed in relation to body composition at 9-15 years of age. In cohort 1, TACSTD2 expression was inversely correlated with methylation (P = 0.016), and both measures were associated with fat mass (expression, P = 0.049; methylation, P = 0.037). Although associated with gene expression (cohort 1, P = 0.008) and methylation (cohort 1, P = 2.98 x 10(-11); cohort 2, P = 3.43 x 10(-15) rs61779296 was not associated with postnatal growth or fat mass in either cohort following multiple regression analysis. Hence, the lack of association between fat mass and a methylation proxy SNP suggests that reverse causation or confounding may explain the initial association between fat mass and gene regulation. Non-causal methylation patterns may still be useful predictors of later adiposity. Diabetes 61:391-400, 2012