title: Dopamine D1 receptor gene variation modulates opioid dependence risk by affecting transition to addiction.
abstract: Dopamine D1 receptor (DRD1) modulates opioid reinforcement, reward, and opioid-induced neuroadaptation. We propose that DRD1 polymorphism affects susceptibility to opioid dependence (OD), the efficiency of transition to OD, and opioid-induced pleasure response. We analyzed potential association between seven DRD1 polymorphisms with the following traits: duration of transition from the first use to dependence (DTFUD), subjective pleasure responses to opioid on first use and post-dependence use, and OD risk in 425 Chinese with OD and 514 healthy controls. DTFUD and level of pleasure responses were examined using a semi-structured interview. The DTFUD of opioid addicts ranged from 5 days to 11 years. Most addicts (64.0%) reported non-comfortable response upon first opioid use, while after dependence, most addicts (53.0%) felt strong opioid-induced pleasure. Survival analysis revealed a correlation of prolonged DTFUD with the minor allele-carrying genotypes of DRD1 rs4532 (hazard ratios (HR) = 0.694; p = 0.001) and rs686 (HR = 0.681, p = 0.0003). Binary logistic regression indicated that rs10063995 GT genotype (vs. GG+TT, OR = 0.261) could predict decreased pleasure response to first-time use and the minor alleles of rs686 (OR = 0.535) and rs4532 (OR = 0.537) could predict decreased post-dependence pleasure. Moreover, rs686 minor allele was associated with a decreased risk for rapid transition from initial use to dependence (DTFUD≤30 days; OR = 0.603) or post-dependence euphoria (OR = 0.603) relative to major allele. In conclusion, DRD1 rs686 minor allele decreases the OD risk by prolonging the transition to dependence and attenuating opioid-induced pleasure in Chinese.
authors: College of Medicine and Forensics, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, People's Republic of China ; Key Laboratory of the Health Ministry for Forensic Sciences, Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China ; Key Laboratory of the Education Ministry for Environment and Genes Related to Diseases, Xi'an, Shaanxi, People's Republic of China.
authors: Feng
authors: F
authors: Zhu
authors: Chun-xia
authors: CX
authors: Yan
authors: Yi-chong
authors: YC
authors: Wen
authors: Jiayin
authors: J
authors: Wang
authors: Jinbo
authors: J
authors: Bi
authors: Ya-ling
authors: YL
authors: Zhao
authors: Lai
authors: L
authors: Wei
authors: Cheng-ge
authors: CG
authors: Gao
authors: Wei
authors: W
authors: Jia
authors: Sheng-bin
authors: SB
authors: Li
mesh_terms: D000328:Adult; D017668:Age of Onset; D000483:Alleles; D016739:Behavior, Addictive / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D009293:Opioid-Related Disorders / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D020641:Polymorphism, Single Nucleotide; D017447:Receptors, Dopamine D1 / Q000235:genetics*; D012306:Risk; D011795:Surveys and Questionnaires; D013997:Time Factors
chemical_list: C583260:DRD1 protein, human; D017447:Receptors, Dopamine D1
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