Ethnic diversity of DNA methylation in the OPRM1 promoter region in lymphocytes of heroin addicts.
Ethnic diversity of DNA methylation in the OPRM1 promoter region in lymphocytes of heroin addicts.
复制标题
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
DOI：
10.1007/s00439-010-0807-6
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发表时间：
2010-06
期刊：
影响因子：
5.3
通讯作者：
Kreek MJ
中科院分区：
文献类型：
--
作者：
Nielsen DA;Hamon S;Yuferov V;Jackson C;Ho A;Ott J;Kreek MJ
μ-阿片受体是许多内源性阿片样物质和阿片类药物的作用部位。我们假设，在特定的CpG二核苷酸的DNA甲基化的差异，前严重的海洛因成瘾者美沙酮维持治疗和对照组将部分取决于种族。对非裔美国人（118例，80例对照）和西班牙裔美国人（142例，61例对照）进行了μ-阿片受体基因（OPRM 1）启动子区域的DNA甲基化分析，并将这些与我们早期研究中的类似高加索队列进行了比较。在对照组中，与西班牙裔或高加索人相比，非洲裔美国人的甲基化水平较高。在三个种族的对照组中，在-25和+12 CpG位点发现了甲基化水平的显着实验差异。与对照组相比，前海洛因依赖者的CpG位点的总体甲基化水平显着升高（逐点P = 0.0457）。然而，在非裔美国人中，甲基化程度在前海洛因成瘾者中在+12 CpG位点上显著降低（P = 0.0032，Bonferroni校正的一般估计方程）。在西班牙裔中，前海洛因成瘾者在-25（P < 0.001，实验方面），-14（P = 0.001，实验方面）和+27（P < 0.001，实验方面）CpG位点的甲基化程度增加。OPRM 1启动子区甲基化的这些变化可能导致美沙酮维持治疗稳定的前海洛因成瘾者淋巴细胞中μ阿片受体基因表达的改变。
The μ-opioid receptor is the site of action of many endogenous opioids as well as opiates. We hypothesize that differences in DNA methylation of specific CpG dinucleotides between former severe heroin addicts in methadone maintenance treatment and control subjects will depend, in part, upon ethnicity. DNA methylation analysis of the μ-opioid receptor gene (OPRM1) promoter region was performed on African-Americans (118 cases, 80 controls) and Hispanics (142 cases, 61 controls) and these were compared with a similar Caucasian cohort from our earlier study. In controls, a higher methylation level was found in the African-Americans compared with the Hispanics or Caucasians. Significant experiment-wise differences in methylation levels were found at the −25 and +12 CpG sites in the controls among the three ethnicities. The overall methylation level of the CpG sites were significantly higher in the former heroin addicts when compared with the controls (point-wise P = 0.0457). However, in the African-Americans, the degree of methylation was significantly decreased experiment-wise in the former heroin addicts at the +12 CpG site (P = 0.0032, Bonferroni corrected general estimating equations). In Hispanics, the degree of methylation was increased in the former heroin addicts at the −25 (P < 0.001, experiment-wise), −14 (P = 0.001, experiment-wise), and +27 (P < 0.001, experiment-wise) CpG sites. These changes in methylation of the OPRM1 promoter region may lead to altered expression of the μ-opioid receptor gene in the lymphocytes of former heroin addicts who are stabilized in methadone maintenance treatment.
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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
影响因子：
15.9
作者：
Alikhani-Koopaei, R;Fouladkou, F;Frey, BM
通讯作者：
Frey, BM
影响因子：
1.8
作者：
Franchina, M;Kay, PH
通讯作者：
Kay, PH
DOI：
10.1073/pnas.0500398102
发表时间：
2005-07-26
影响因子：
11.1
作者：
Fraga, MF;Ballestar, E;Esteller, M
通讯作者：
Esteller, M
影响因子：
3.3
作者：
Boensch, D.;Lenz, B.;Bleich, S.
通讯作者：
Bleich, S.