Correlation of global and gene-specific DNA methylation in maternal-infant pairs.
Correlation of global and gene-specific DNA methylation in maternal-infant pairs.
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DOI：
10.1371/journal.pone.0013730
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发表时间：
2010-10-29
期刊：
影响因子：
3.7
通讯作者：
Christiani DC
中科院分区：
文献类型：
--
作者：
Kile ML;Baccarelli A;Tarantini L;Hoffman E;Wright RO;Christiani DC
DNA甲基化模式的遗传是一种流行的理论，用来解释父母的遗传和环境因素对其后代表型的影响，但很少有研究在人类中研究这种关系。使用从孟加拉国前瞻性出生队列中随机选择的120对母亲-脐带血样本，我们通过焦磷酸测序p16启动子区域中的7个CpG位置，p53，LINE-1和Alu启动子区域中的4个CpG位置来定量DNA甲基化。在p16、LINE-1和Alu而不是p53上观察到母体和脐带血之间的正相关性。多元线性回归模型观察到LINE-1和Alu的母体和脐带血之间存在显著相关性（LINE-1：β = 0.63，p<0.0001; Alu：β = 0.28，p = 0.009）。 校正多重比较后，母亲p16第4位甲基化显著预测了脐带血中相同位置的甲基化（β = 0.43，p =<0.0001）。 这些模型分别解释了LINE-1、Alu和p16第4位脐带%5mC观察到的变异性的48%、5%和16%。这些结果表明，母亲血液中的DNA甲基化与她的后代在LINE-1，Alu和p16，而不是p53相关。需要进一步的研究来确认这些观察到的关联是由于表观遗传事件的遗传还是母亲和胎儿之间的共享环境。未来的研究还应该使用基于多代家庭的设计，量化母亲和父亲对后代DNA甲基化的贡献。
The inheritance of DNA methylation patterns is a popular theory to explain the influence of parental genetic and environmental factors on the phenotype of their offspring but few studies have examined this relationship in humans. Using 120 paired maternal-umbilical cord blood samples randomly selected from a prospective birth cohort in Bangladesh, we quantified DNA methylation by pyrosequencing seven CpG positions in the promoter region of p16, four CpG positions in the promoter region of p53, LINE-1 and Alu. Positive correlations were observed between maternal and umbilical cord blood at p16, LINE-1, and Alu but not p53. Multiple linear regression models observed a significant association between maternal and umbilical cord blood at LINE-1 and Alu (LINE-1: β = 0.63, p<0.0001; Alu: β = 0.28, p = 0.009). After adjusting for multiple comparisons, maternal methylation of p16 at position 4 significantly predicted methylation at the same position in umbilical cord blood (β = 0.43, p = <0.0001). These models explained 48%, 5% and 16% of the observed variability in umbilical cord %5mC for LINE-1, Alu and p16 at position 4, respectively. These results suggest that DNA methylation in maternal blood was correlated with her offspring at LINE-1, Alu, and p16 but not p53. Additional studies are needed to confirm whether these observed associations were due to the inheritance of epigenetic events or the shared environment between mother and fetus. Future studies should also use a multi-generational family-based design that would quantify both maternal and paternal contributions to DNA methylation in offspring across more than one generation.
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