TY - JOUR AB - Heroin and methylamphetamine (METH) are two addictive drugs that cause serious problems for society. Dopamine receptor D4 (DRD4), a key receptor in the dopaminergic system, may facilitate the development of drug addiction. The aim of the present study was to investigate the association between the promoter methylation level of DRD4 gene and drug addiction. Bisulfite pyrosequencing technology was used to measure the methylation levels of DRD4 promoter in 60 drug addicts and 52 matched controls. Significantly higher levels of DRD4 CpG1 and CpG4 methylation were detected in METH and heroin drug addicts compared with controls (P<0.05). Male METH addicts exhibited significantly higher DRD4 CpG1, CpG2 and CpG4 methylation levels compared with sex‑matched controls (P<0.05). In heroin addicts, a positive correlation was observed between depression‑dejection and DRD4 CpG5 methylation (r=0.537, P=0.039) whereas there was a negative correlation between drug usage frequency and CpG1 methylation (r=‑0.632, P=0.011). In METH addicts, methylation levels were not significantly associated with depression‑dejection and drug usage frequency. In addition, luciferase assays demonstrated that the target sequence of the DRD4 promoter upregulates gene expression. The results of the present study suggest that DNA methylation of DRD4 may be responsible for the pathophysiology of drug addiction. AD - Medical Genetics Center, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, P.R. China Laboratory of Behavioral Neuroscience, Ningbo Addiction Research and Treatment Center, Ningbo, Zhejiang 315010, P.R. China AU - Ji,Huihui AU - Xu,Xuting AU - Liu,Guili AU - Liu,Huifen AU - Wang,Qinwen AU - Shen,Wenwen AU - Li,Longhui AU - Xie,Xiaohu AU - Hu,Haochang AU - Xu,Lei AU - Zhou,Wenhua AU - Duan,Shiwei DA - 2018/02/01 DO - 10.3892/etm.2017.5615 EP - 2133 IS - 2 JO - Exp Ther Med PY - 2018 SN - 1792-0981 1792-1015 SP - 2128 ST - Dopamine receptor D4 promoter hypermethylation increases the risk of drug addiction T2 - Experimental and Therapeutic Medicine TI - Dopamine receptor D4 promoter hypermethylation increases the risk of drug addiction UR - https://doi.org/10.3892/etm.2017.5615 VL - 15 ER -