Epigenetic variation in the mu-opioid receptor gene in infants with neonatal abstinence syndrome.
Epigenetic variation in the mu-opioid receptor gene in infants with neonatal abstinence syndrome.
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DOI：
10.1016/j.jpeds.2014.05.040
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发表时间：
2014-09
影响因子：
5.1
通讯作者：
Davis, Jonathan M.
中科院分区：
文献类型：
--
作者：
Wachman, Elisha M.;Hayes, Marie J.;Lester, Barry M.;Terrin, Norma;Brown, Mark S.;Nielsen, David A.;Davis, Jonathan M.
宫内阿片类药物暴露引起的新生儿戒断综合征（NAS）具有高度可变性，遗传因素似乎起着重要作用。胞嘧啶：鸟嘌呤（CpG）二核苷酸甲基化的表观遗传学变化可以在药物暴露后发生，并可能有助于解释NAS变异性。我们将暴露于阿片类药物的婴儿中μ阿片受体（OPRM 1）启动子的DNA甲基化水平与NAS结果相关。根据机构方案，对86名接受NAS治疗的婴儿的脐带血或唾液DNA样本进行了分析。测定16个OPRM 1 CpG位点的甲基化水平，并将其与NAS结果指标相关，包括治疗需求、>2种药物治疗和住院时间。我们调整了协变量和多重基因检测。65%的婴儿需要治疗NAS，24%需要≥2种药物。在接受治疗的婴儿与未接受治疗的婴儿中，在-10 CpG处测量OPRM 1启动子的超甲基化[校正差异δ=3.2%（95% CI 0.3-6.0%），p=0.03;多重检验校正后NS]。在-14 [δ=4.9%]处存在高甲基化（95% CI 1.8-8.1%），p=0.003]，−10 [δ=5.0%（95% CI 2.3-7.7%），p=0.0005）]和+84 [δ=3.5%（95%CI 0.6 - 6.4），p=0.02]需要≥2种药物的婴儿中的CpG位点在多次测试校正后在-14和-10仍然显着。OPRM 1启动子内甲基化的增加与更差的NAS结果相关，与基因沉默一致。
Neonatal abstinence syndrome (NAS) from in utero opioid exposure is highly variable with genetic factors appearing to play an important role. Epigenetic changes in cytosine:guanine (CpG) dinucleotide methylation can occur after drug exposure and may help to explain NAS variability. We correlated DNA methylation levels in the mu-opioid receptor (OPRM1) promoter in opioid-exposed infants and correlate them with NAS outcomes. DNA samples from cord blood or saliva were analyzed for 86 infants being treated for NAS according to institutional protocol. Methylation levels at 16 OPRM1 CpG sites were determined and correlated with NAS outcome measures, including need for treatment, treatment with >2 medications, and length of hospital stay. We adjusted for co-variates and multiple genetic testing. Sixty-five percent of infants required treatment for NAS, and 24% required ≥2 medications. Hypermethylation of the OPRM1 promoter was measured at the −10 CpG in treated versus non-treated infants [adjusted difference δ=3.2% (95% CI 0.3–6.0%), p=0.03; NS after multiple testing correction]. There was hypermethylation at the −14 [δ=4.9% (95% CI 1.8–8.1%), p=0.003], −10 [δ=5.0% (95% CI 2.3–7.7%), p=0.0005)], and +84 [δ=3.5% (95% CI 0.6 – 6.4), p=0.02] CpG sites in infants requiring ≥2 medications which remained significant for −14 and −10 after multiple testing correction. Increased methylation within the OPRM1 promoter is associated with worse NAS outcomes, consistent with gene silencing.
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影响因子：
5.3
作者：
Levran O;Yuferov V;Kreek MJ
通讯作者：
Kreek MJ
影响因子：
3.4
作者：
Byrnes, John J.;Johnson, Nicole L.;Carini, Lindsay M.;Byrnes, Elizabeth M.
通讯作者：
Byrnes, Elizabeth M.
DOI：
10.1073/pnas.1018699108
发表时间：
2011-05-31
影响因子：
11.1
作者：
Ray, Riju;Ruparel, Kosha;Lerman, Caryn
通讯作者：
Lerman, Caryn
海洛因成瘾者淋巴细胞OPRM1启动子区DNA甲基化的种族多样性
影响因子：
5.3
作者：
Nielsen DA;Hamon S;Yuferov V;Jackson C;Ho A;Ott J;Kreek MJ
通讯作者：
Kreek MJ
DOI：
10.1016/j.bbrc.2006.12.151
发表时间：
2007-03-02
影响因子：
3.1
作者：
Douet, Vanessa;Heller, Matthew B.;Le Saux, Olivier
通讯作者：
Le Saux, Olivier