title: Postnatal growth and DNA methylation are associated with differential gene expression of the TACSTD2 gene and childhood fat mass.
abstract: 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.
authors.affiliation: Institute of Genetic Medicine and Human Nutrition Research Centre, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Groom
authors.forename: Catherine
authors.initials: C
authors.lastname: Potter
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Swan
authors.forename: Ghazaleh
authors.initials: G
authors.lastname: Fatemifar
authors.forename: David M
authors.initials: DM
authors.lastname: Evans
authors.forename: Susan M
authors.initials: SM
authors.lastname: Ring
authors.forename: Valerie
authors.initials: V
authors.lastname: Turcot
authors.forename: Mark S
authors.initials: MS
authors.lastname: Pearce
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Embleton
authors.forename: George Davey
authors.initials: GD
authors.lastname: Smith
authors.forename: John C
authors.initials: JC
authors.lastname: Mathers
authors.forename: Caroline L
authors.initials: CL
authors.lastname: Relton
mesh_terms: D050154:Adiposity; D000293:Adolescent; D000951:Antigens, Neoplasm / Q000235:genetics*; D001823:Body Composition; D001835:Body Weight; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002648:Child; D002657:Child Development; D015331:Cohort Studies; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499380:TACSTD2 protein, human