To study the potential role of brain-derived neurotrophic factor (BDNF) methylation in heroin addiction, we first detected the methylation level of seven CpG islands that included 106 CpG sites in the promoter regions of BDNF from 120 people addicted to heroin and 113 controls. Methylation quantitative trait locus (mQTL) analysis was then employed to determine the association between the single-nucleotide polymorphism rs6265, a well-known locus shown to be correlated with heroin addiction, and the methylation levels of these CpG sites. Finally, we used the JASPAR database to predict whether transcription factors could bind to these CpG sites. We found that the methylation levels of CpG islands 6 and 7 and the methylation levels of BDNF_45 and BDNF_80 were significantly higher in the heroin addiction group than in the control group. We also found that rs6265 was an mQTL and was associated with the methylation level of BDNF_58. Using the JASPAR database, we found that ALX homeobox 3 (ALX3), achaete-scute family bHLH transcription factor 1 (ASCL1) and aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) could bind to CpG island 6, and ALX3 could bind to CpG island 7. In summary, we showed that increased DNA methylation in the promoter regions of the BDNF gene was associated with heroin addiction in Han Chinese.

为了研究脑源性神经营养因子 ( BDNF ) 甲基化在海洛因成瘾中的潜在作用，我们首先检测了120 名海洛因成瘾者和 113 名对照组的 7 个 CpG 岛的甲基化水平，其中包括BDNF启动子区域中的 106 个 CpG 位点。然后使用甲基化数量性状基因座 (mQTL) 分析来确定单核苷酸多态性 rs6265（一个与海洛因成瘾相关的众所周知的基因座）与这些 CpG 位点的甲基化水平之间的关联。最后，我们使用 JASPAR 数据库预测转录因子是否可以与这些 CpG 位点结合。我们发现CpG岛6和7的甲基化水平以及BDNF_45和BDNF的甲基化水平_海洛因成瘾组的 80 人明显高于对照组。我们还发现 rs6265 是一个 mQTL，并且与 BDNF_58 的甲基化水平相关。使用JASPAR数据库，我们发现 ALX 同源框 3 (ALX3)、achaete-scute family bHLH 转录因子 1 (ASCL1) 和芳烃受体核转位子 2 (ARNT2) 可以与 CpG 岛 6 结合，ALX3 可以与 CpG 岛 7 结合。 总之，我们发现BDNF基因启动子区域的 DNA 甲基化增加与汉族海洛因成瘾有关。