Fransquet Peter D, Hutchinson Delyse, Olsson Craig A, Allsop Steve, Elliott Elizabeth J, Burns Lucinda, Mattick Richard, Saffery Richard, Ryan Joanne
a Murdoch Childrens Research Institute, The University of Melbourne , Parkville , Victoria , Australia.
b Department of Paediatrics , University of Melbourne, Royal Children's Hospital , Melbourne , Australia.
Am J Drug Alcohol Abuse. 2017 Nov;43(6):671-677. doi: 10.1080/00952990.2017.1314488. Epub 2017 Apr 27.
Maternal cannabis use in pregnancy is linked with long-term adverse behavioral outcomes in offspring. Epigenetic processes established in utero that affect dopaminergic (reward) signaling may mediate risks. Associations between cannabis use and offspring DNA methylation have not been investigated; however, maternal tobacco smoking in pregnancy is associated with distinct patterns of DNA methylation at birth and beyond.
To determine whether maternal cannabis use is associated with methylation of the dopamine receptor gene DRD4 promoter in infants.
Mothers in the Triple B study provided detailed information on drug use in each trimester of pregnancy. Buccal swabs were collected from neonates at 8 weeks (n = 804, 51.7% male, and 48.3% female). DRD4 promoter DNA methylation was measured using SEQUENOM MassARRAY.
Fifty-seven of the women in the study reported drug use during pregnancy, of whom 44 used cannabis. Of 19 cytosine-phosphate-guanine dinucleotides (CpG) units tested in DRD4, gestational cannabis use was associated with offspring methylation at 1 CpG unit in multivariate models (β + 1.48, CI: 0.02 to 2.93, and p = 0.047). At another site there was weak evidence that both cannabis and other drug use were independently associated with increased methylation, while the association with tobacco was in the reverse direction (cannabis use β + 0.67, CI: -0.12 to 1.46, and p = 0.09; other drug use β + 1.11, CI: 0.17 to 2.05, and p = 0.02; tobacco use β -0.41, CI: -0.85 to 0.03, and p = 0.07). None of the associations would remain significant after correction for multiple testing.
There is no strong evidence that maternal cannabis use in pregnancy is associated with offspring DRD4 methylation.
孕期母亲使用大麻与后代长期不良行为后果有关。子宫内建立的影响多巴胺能（奖赏）信号传导的表观遗传过程可能介导风险。大麻使用与后代DNA甲基化之间的关联尚未得到研究；然而，孕期母亲吸烟与出生时及之后不同的DNA甲基化模式有关。
确定孕期母亲使用大麻是否与婴儿多巴胺受体基因DRD4启动子的甲基化有关。
“三B研究”中的母亲提供了孕期各阶段药物使用的详细信息。在婴儿8周时采集颊拭子（n = 804，男51.7%，女48.3%）。使用SEQUENOM MassARRAY测量DRD4启动子DNA甲基化。
研究中的57名女性报告在孕期使用过药物，其中44人使用过大麻。在DRD4中测试的19个胞嘧啶-磷酸-鸟嘌呤二核苷酸（CpG）单元中，在多变量模型中，孕期使用大麻与后代1个CpG单元的甲基化有关（β + 1.48，CI：0.02至2.93，p = 0.047）。在另一个位点，有微弱证据表明大麻和其他药物使用均与甲基化增加独立相关，而与烟草的关联方向相反（大麻使用β + 0.67，CI：-0.12至1.46，p = 0.09；其他药物使用β + 1.11，CI：0.17至2.05，p = 0.02；烟草使用β -0.41，CI：-0.85至0.03，p = 0.07）。经过多重检验校正后，这些关联均不再显著。
没有充分证据表明孕期母亲使用大麻与后代DRD4甲基化有关。
