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 × 10−11; cohort 2, P = 3.43 × 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. Noncausal methylation patterns may still be useful predictors of later adiposity.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db11-1039/-/DC1.
The funders had no role in study design, data collection, analysis, the decision to publish, or the preparation of the manuscript.
- Received July 29, 2011.
- Accepted November 10, 2011.
- © 2012 by the American Diabetes Association.
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