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Childhood Bone Mineral Content Is Associated With Methylation Status of the RXRA Promoter at Birth
Author(s) -
Harvey Nicholas C,
Sheppard Allan,
Godfrey Keith M,
McLean Cameron,
Garratt Emma,
Ntani Georgia,
Davies Lucy,
Murray Robert,
Inskip Hazel M,
Gluckman Peter D,
Hanson Mark A,
Lillycrop Karen A,
Cooper Cyrus
Publication year - 2014
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.2056
Subject(s) - offspring , vitamin d and neurology , cpg site , dna methylation , cohort , medicine , physiology , vitamin d deficiency , population , endocrinology , methylation , cord blood , pregnancy , biology , genetics , environmental health , gene expression , gene
Maternal vitamin D deficiency has been associated with reduced offspring bone mineral accrual. Retinoid‐X receptor‐alpha (RXRA) is an essential cofactor in the action of 1,25‐dihydroxyvitamin D (1,25[OH] 2 ‐vitamin D), and RXRA methylation in umbilical cord DNA has been associated with later offspring adiposity. We tested the hypothesis that RXRA methylation in umbilical cord DNA collected at birth is associated with offspring skeletal development, assessed by dual‐energy X‐ray absorptiometry, in a population‐based mother‐offspring cohort (Southampton Women's Survey). Relationships between maternal plasma 25‐hydroxyvitamin D (25[OH]‐vitamin D) concentrations and cord RXRA methylation were also investigated. In 230 children aged 4 years, a higher percent methylation at four of six RXRA CpG sites measured was correlated with lower offspring bone mineral content (BMC) corrected for body size (β = −2.1 to −3.4 g/SD, p = 0.002 to 0.047). In a second independent cohort ( n = 64), similar negative associations at two of these CpG sites, but positive associations at the two remaining sites, were observed; however, none of the relationships in this replication cohort achieved statistical significance. The maternal free 25(OH)‐vitamin D index was negatively associated with methylation at one of these RXRA CpG sites (β = −3.3 SD/unit, p = 0.03). Thus, perinatal epigenetic marking at the RXRA promoter region in umbilical cord was inversely associated with offspring size–corrected BMC in childhood. The potential mechanistic and functional significance of this finding remains a subject for further investigation. © 2014 American Society for Bone and Mineral Research.