DNA methylation patterns in cord blood DNA and body size in childhood.
DNA methylation patterns in cord blood DNA and body size in childhood.
复制标题
DOI：
10.1371/journal.pone.0031821
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Davey Smith G
中科院分区：
文献类型：
--
作者：
Relton CL;Groom A;St Pourcain B;Sayers AE;Swan DC;Embleton ND;Pearce MS;Ring SM;Northstone K;Tobias JH;Trakalo J;Ness AR;Shaheen SO;Davey Smith G
在早期生命中获得的表观遗传标记可能通过其在转录调控中的作用在以后的发育中具有表型后果，所述转录调控与包括肥胖症在内的疾病的发育起源相关。这项研究的目的是调查出生时的DNA甲基化水平是否与儿童后期的体型有关。使用涉及两个出生队列的研究设计进行转录谱分析，然后进行外周血中的DNA甲基化分析。在24名个体中进行基因表达分析，其生物样品和临床数据在平均±标准差（SD）12.35（0.95）岁时收集，将体重指数（BMI）的上三分位数和下三分位数与平均（SD）BMI差异9.86（2.37）kg/m2进行比较。这产生了一组差异表达的基因，用于DNA甲基化分析，然后在178个个体的脐带血DNA中进行甲基化分析，这些个体的身体组成数据在平均（SD）年龄9.83（0.23）岁时前瞻性收集。分析了29个差异表达基因（>1.2倍且p<10−4），以确定每个基因1-3个位点的DNA甲基化水平。5个基因未甲基化，其余24个基因的DNA甲基化使用线性回归与bootstrapping进行分析。研究的24个基因中有9个（37.5%）的甲基化与9岁时的至少一个身体组成指数（BMI，脂肪量，瘦体重，身高）相关，尽管在多次测试校正后这些关联中只有一个仍然存在（ALPL与身高，p校正= 0.017）。 脐带血中的DNA甲基化模式与儿童时期基因表达、体型和组成的改变有一定的关联。所观察到的关系是相关的，尽管建议在子宫内生活和以后的表型之间的机械表观遗传联系，需要进一步的调查，以建立因果关系。
Epigenetic markings acquired in early life may have phenotypic consequences later in development through their role in transcriptional regulation with relevance to the developmental origins of diseases including obesity. The goal of this study was to investigate whether DNA methylation levels at birth are associated with body size later in childhood. A study design involving two birth cohorts was used to conduct transcription profiling followed by DNA methylation analysis in peripheral blood. Gene expression analysis was undertaken in 24 individuals whose biological samples and clinical data were collected at a mean ± standard deviation (SD) age of 12.35 (0.95) years, the upper and lower tertiles of body mass index (BMI) were compared with a mean (SD) BMI difference of 9.86 (2.37) kg/m2. This generated a panel of differentially expressed genes for DNA methylation analysis which was then undertaken in cord blood DNA in 178 individuals with body composition data prospectively collected at a mean (SD) age of 9.83 (0.23) years. Twenty-nine differentially expressed genes (>1.2-fold and p<10−4) were analysed to determine DNA methylation levels at 1–3 sites per gene. Five genes were unmethylated and DNA methylation in the remaining 24 genes was analysed using linear regression with bootstrapping. Methylation in 9 of the 24 (37.5%) genes studied was associated with at least one index of body composition (BMI, fat mass, lean mass, height) at age 9 years, although only one of these associations remained after correction for multiple testing (ALPL with height, p Corrected = 0.017). DNA methylation patterns in cord blood show some association with altered gene expression, body size and composition in childhood. The observed relationship is correlative and despite suggestion of a mechanistic epigenetic link between in utero life and later phenotype, further investigation is required to establish causality.
登录
查看更多内容
影响因子：
3.7
作者：
Kile ML;Baccarelli A;Tarantini L;Hoffman E;Wright RO;Christiani DC
通讯作者：
Christiani DC
DOI：
10.1097/ede.0b013e3181f20457
发表时间：
2010-11
期刊：
Epidemiology (Cambridge, Mass.)
影响因子：
--
作者：
Baccarelli A;Wright R;Bollati V;Litonjua A;Zanobetti A;Tarantini L;Sparrow D;Vokonas P;Schwartz J
通讯作者：
Schwartz J
影响因子：
3.6
作者：
Lewis, Sarah J.;Leary, Sam;Ness, Andy
通讯作者：
Ness, Andy
影响因子：
9.8
作者：
Glowinska-Olszewska, Barbara;Urban, Miroslawa
通讯作者：
Urban, Miroslawa
影响因子：
3.5
作者：
Bouret, S. G.;Simerly, R. B.
通讯作者：
Simerly, R. B.