海洛因成瘾者淋巴细胞中 OPRM1 启动子区域 DNA 甲基化的种族多样性。
Ethnic diversity of DNA methylation in the OPRM1 promoter region in lymphocytes of heroin addicts.
机构信息
Laboratory of the Biology of Addictive Diseases, The Rockefeller University, Box 171, 1230 York Avenue, New York 10065, USA.
出版信息
Hum Genet. 2010 Jun;127(6):639-49. doi: 10.1007/s00439-010-0807-6. Epub 2010 Mar 18.
The mu-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 mu-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 mu-opioid receptor gene in the lymphocytes of former heroin addicts who are stabilized in methadone maintenance treatment.
阿片受体是许多内源性阿片肽以及鸦片类药物的作用靶点。我们假设，在接受美沙酮维持治疗的前重度海洛因成瘾者与对照组之间，特定 CpG 二核苷酸的 DNA 甲基化差异部分取决于种族。对非洲裔美国人（118 例，80 例对照）和西班牙裔美国人（142 例，61 例对照）的阿片受体基因（OPRM1）启动子区域的 DNA 甲基化分析与我们之前研究中的类似白人群体进行了比较。在对照组中，与西班牙裔或白种人相比，非洲裔美国人的甲基化水平更高。在三个种族的对照组中，-25 和+12 CpG 位点的甲基化水平存在显著的实验差异。与对照组相比，前海洛因成瘾者的 CpG 位点总体甲基化水平显著升高（逐点 P = 0.0457）。然而，在非洲裔美国人中，前海洛因成瘾者的+12 CpG 位点的甲基化程度在实验上显著降低（P = 0.0032，Bonferroni 校正的一般估计方程）。在西班牙裔中，前海洛因成瘾者的-25（P < 0.001，实验上）、-14（P = 0.001，实验上）和+27（P < 0.001，实验上）CpG 位点的甲基化程度增加。阿片受体基因启动子区域的这种甲基化变化可能导致接受美沙酮维持治疗的前海洛因成瘾者的淋巴细胞中阿片受体基因表达发生改变。
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