Perinatal maternal alcohol consumption and methylation of the dopamine receptor DRD4 in the offspring: the Triple B study.
Perinatal maternal alcohol consumption and methylation of the dopamine receptor DRD4 in the offspring: the Triple B study.
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DOI：
10.1093/eep/dvw023
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发表时间：
2016-12
影响因子：
3.8
通讯作者：
Triple B Research Consortium
中科院分区：
文献类型：
--
作者：
Fransquet PD;Hutchinson D;Olsson CA;Wilson J;Allsop S;Najman J;Elliott E;Mattick RP;Saffery R;Ryan J;Triple B Research Consortium
母亲在围产期饮酒是一个重大的公共卫生问题，其严重程度与胎儿酒精谱系障碍和后代的一系列不良健康结果有关。潜在的分子机制在很大程度上仍然未知，但可能包括发育过程中基因活性的表观遗传破坏。酒精直接激活神经递质多巴胺，它在神经发育中起着至关重要的作用。探讨产前和产后早期饮酒是否与婴儿多巴胺受体 DRD4 启动子甲基化差异相关 (n = 844)。数据来自基于大量人群的 Triple B 妊娠队列研究，其中包含妊娠每个三个月和产后早期母亲饮酒量的详细信息。从 8 周时收集的婴儿口腔拭子中提取 DNA。通过 Sequenom MassARRAY 分析 DRD4 启动子 DNA 甲基化。没有强有力的证据表明怀孕期间饮酒与产后 8 周婴儿 DRD4 甲基化之间存在关联。然而，产后 8 周同时评估的母亲饮酒量与检查的 19 个 CpG 单位中的 13 个甲基化增加相关（最大 Δ + 3.20%，95%置信区间：1.66,4.75%，CpG.6 时 P = 0.0001）。这种关联在母乳喂养的女性中最为明显，这表明酒精暴露可能通过母乳产生直接影响。这项研究的结果可能会影响有关母乳喂养母亲饮酒的公共卫生指南；然而，还需要进一步的研究来证实这些新发现。
Maternal alcohol use during the perinatal period is a major public health issue, the higher ends of which are associated with foetal alcohol spectrum disorder and a range of adverse health outcomes in the progeny. The underlying molecular mechanisms remain largely unknown but may include the epigenetic disruption of gene activity during development. Alcohol directly activates the neurotransmitter dopamine, which plays an essential role in neurodevelopment. To investigate whether antenatal and early postnatal alcohol consumption were associated with differential dopamine receptor DRD4 promoter methylation in infants (n = 844). Data were drawn from the large population based Triple B pregnancy cohort study, with detailed information on maternal alcohol consumption in each trimester of pregnancy and early postpartum. DNA was extracted from infant buccal swabs collected at 8-weeks. DRD4 promoter DNA methylation was analysed by Sequenom MassARRAY. No strong evidence was found for an association between alcohol consumption during pregnancy and infant DRD4 methylation at 8-weeks postpartum. However, maternal alcohol consumption assessed contemporaneously at 8-weeks postpartum was associated with increased methylation at 13 of 19 CpG units examined (largest Δ + 3.20%, 95%Confidence Interval:1.66,4.75%, P = 0.0001 at CpG.6). This association was strongest in women who breastfeed, suggesting the possibility of a direct effect of alcohol exposure via breast milk. The findings of this study could influence public health guidelines around alcohol consumption for breastfeeding mothers; however, further research is required to confirm these novel findings.