Postnatal Growth and DNA Methylation Are Associated With Differential Gene Expression of the TACSTD2 Gene and Childhood Fat Mass
- Alexandra Groom1,
- Catherine Potter1,
- Daniel C. Swan2,
- Ghazaleh Fatemifar3,
- David M. Evans3,
- Susan M. Ring4,
- Valerie Turcot5,
- Mark S. Pearce6,
- Nicholas D. Embleton6,7,
- George Davey Smith3,
- John C. Mathers8 and
- Caroline L. Relton1⇓
- 1Institute of Genetic Medicine and Human Nutrition Research Centre, Newcastle University, Newcastle upon Tyne, U.K.
- 2Bioinformatics Support Unit, Newcastle University, Newcastle upon Tyne, U.K.
- 3Medical Research Council Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, U.K.
- 4School of Social and Community Medicine, University of Bristol, Bristol, U.K.
- 5Institute of Nutraceuticals and Functional Foods, Laval University, Quebec, Canada
- 6Institute of Health and Society, Newcastle University, Newcastle upon Tyne, U.K.
- 7Newcastle Neonatal Service, Royal Victoria Infirmary, Newcastle upon Tyne, U.K.
- 8Institute for Ageing and Health, Human Nutrition Research Centre, Newcastle University, Newcastle upon Tyne, U.K.
- Corresponding author: Caroline L. Relton, .
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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