McLaughlin Poppy, Mactier Helen, Gillis Cheryl, Hickish Tamas, Parker Anton, Liang Wei-Jun, Osselton M David
Department of Archaeology, Anthropology, and Forensic Science, Bournemouth University, Poole, United Kingdom.
Neonatal Unit, Princess Royal Maternity, Glasgow, United Kingdom.
J Pediatr. 2017 Nov;190:180-184.e1. doi: 10.1016/j.jpeds.2017.07.026. Epub 2017 Sep 1.
To investigate whether in utero opioid exposure, which has been linked to adverse neurodevelopmental and social outcomes, is associated with altered DNA methylation of opioid-related genes at birth.
Observational cohort study of 21 healthy methadone-maintained opioid-dependent mother-infant dyads consecutively delivered at >36 weeks of gestation, and 2 comparator groups: smoking, "deprived" opioid-naïve mother-infant dyads (n = 17) and nonsmoking, "affluent" opioid-naïve mother-infant dyads (n = 15). DNA methylation of ABCB1, CYP2D6, and OPRM1 genes for mothers and babies was determined from buccal swabs. Plasma methadone concentrations were additionally measured for methadone-maintained opioid-dependent mothers.
DNA methylation for ABCB1 and CYP2D6 was similar in opioid-naïve infants compared with their mothers, but was less for OPRM1 (3 ± 1.6% vs 8 ± 1%, P < .0005). Opioid-exposed newborns had similar DNA methylation to their mothers for all genes studied and greater methylation of ABCB1 (18 ± 4.8% vs 3 ± 0.5%), CYP2D6 (92 ± 1.2% vs 89 ± 2.4%), and OPRM1 (8 ± 0.3% vs 3 ± 1.6%) compared with opioid-naïve newborns (P < .0005 for all 3 genes). Infant DNA methylation was not related to birth weight, length of hospital stay, maternal smoking, dose or plasma concentration of methadone at delivery, or postcode of residence.
In utero exposure to opioids is associated with increased methylation of opioid-related genes in the newborn infant. It is not clear whether these findings are due to opioid exposure per se or other associated lifestyle factors.
探讨子宫内阿片类药物暴露（这已与不良神经发育和社会结局相关联）是否与出生时阿片类相关基因的DNA甲基化改变有关。
对21对在妊娠>36周时连续分娩的健康美沙酮维持治疗的阿片类药物依赖母婴二元组进行观察性队列研究，以及2个对照群组：吸烟的、“贫困”的未接触阿片类药物的母婴二元组（n = 17）和不吸烟的、“富裕”的未接触阿片类药物的母婴二元组（n = 15）。从口腔拭子中测定母亲和婴儿ABCB1、CYP2D6和OPRM1基因的DNA甲基化情况。另外测定了接受美沙酮维持治疗的阿片类药物依赖母亲的血浆美沙酮浓度。
未接触阿片类药物的婴儿中，ABCB1和CYP2D6的DNA甲基化与其母亲相似，但OPRM1的DNA甲基化较少（3±1.6%对8±1%，P <.0005）。与未接触阿片类药物的新生儿相比，接触阿片类药物的新生儿在所研究的所有基因上与母亲的DNA甲基化相似，且ABCB1（18±4.8%对3±0.5%）、CYP2D6（92±1.2%对89±2.4%）和OPRM1（8±0.3%对3±1.6%）的甲基化程度更高（所有3个基因P均<.0005）。婴儿的DNA甲基化与出生体重、住院时间、母亲吸烟情况、分娩时美沙酮剂量或血浆浓度或居住邮政编码无关。
子宫内阿片类药物暴露与新生儿阿片类相关基因甲基化增加有关。尚不清楚这些发现是由于阿片类药物暴露本身还是其他相关生活方式因素所致。
