Evaluation of Methylation Status of the eNOS Promoter at Birth in Relation to Childhood Bone Mineral Content
Evaluation of Methylation Status of the eNOS Promoter at Birth in Relation to Childhood Bone Mineral Content
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DOI：
10.1007/s00223-011-9554-5
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发表时间：
2012-02-01
影响因子：
4.2
通讯作者：
Cooper, Cyrus
中科院分区：
文献类型：
--
作者：
Harvey, Nicholas C.;Lillycrop, Karen A.;Cooper, Cyrus
我们以前的工作已经表明，儿童肥胖症和围产期脐带组织中几个基因的甲基化状态之间存在关联，包括内皮型一氧化氮合酶（eNOS）。越来越多的证据表明，eNOS在骨代谢中很重要，因此，我们将一组9岁儿童储存脐带中eNOS基因启动子的甲基化状态与儿童骨大小和密度相关。我们使用Sequenom MassARRAY来评估eNOS启动子中两个CpG的甲基化状态，这两个CpG是从我们以前的研究中鉴定的，在储存的66名儿童的脐带中，这些儿童形成了南安普顿出生队列的一部分，并且在9岁时测量了骨大小和密度（Lunar DPXL DXA仪器）。受试者之间的甲基化百分比差异很大。对于两个CpG之一，eNOS chr7：150315553？，在考虑年龄和性别后，甲基化状态与儿童9岁时的全身骨面积（r = 0.28，P = 0.02）、骨矿物质含量（r = 0.34，P = 0.005）和面积骨矿物质密度（r = 0.34，P = 0.005）之间存在强正相关。这些协会是独立的先前记录的后代骨量的母亲决定因素。我们的研究结果表明，eNOS启动子内的特定CpG在出生时的甲基化状态与儿童期骨矿物质含量之间存在关联。这支持eNOS在骨生长和代谢中的作用，并意味着其贡献可能至少部分发生在早期骨骼发育期间。
Our previous work has shown associations between childhood adiposity and perinatal methylation status of several genes in umbilical cord tissue, including endothelial nitric oxide synthase (eNOS). There is increasing evidence that eNOS is important in bone metabolism; we therefore related the methylation status of the eNOS gene promoter in stored umbilical cord to childhood bone size and density in a group of 9-year-old children. We used Sequenom MassARRAY to assess the methylation status of two CpGs in the eNOS promoter, identified from our previous study, in stored umbilical cords of 66 children who formed part of a Southampton birth cohort and who had measurements of bone size and density at age 9 years (Lunar DPXL DXA instrument). Percentage methylation varied greatly between subjects. For one of the two CpGs, eNOS chr7:150315553 ?, after taking account of age and sex, there were strong positive associations between methylation status and the child's whole-body bone area (r = 0.28, P = 0.02), bone mineral content (r = 0.34, P = 0.005), and areal bone mineral density (r = 0.34, P = 0.005) at age 9 years. These associations were independent of previously documented maternal determinants of offspring bone mass. Our findings suggest an association between methylation status at birth of a specific CpG within the eNOS promoter and bone mineral content in childhood. This supports a role for eNOS in bone growth and metabolism and implies that its contribution may at least in part occur during early skeletal development.