Effect of mu-opioid receptor gene polymorphisms on heroin-induced subjective responses in a Chinese population.
BACKGROUND
Genetic factors that influence subjective responses to drug use (such as euphoria) contribute to the risk of addiction. mu-opioid receptor is the molecular target of heroin mediating its effects in both pain relief and euphoria.


METHODS
To evaluate the association of mu-opioid receptor gene (OPRM1) variants with heroin-induced positive responses on first use, we studied 336 Chinese Han heroin addicts recruited in Shanghai and divided heroin addicts into two groups (positive vs. negative) according to the self-reporting feeling on first use. Association analyses with the genotypes and alleles in nine tagging single nucleotide polymorphisms (tSNPs) in OPRM1 with subjective responses were performed. Similar analysis with haplotypes of these tSNPs was also performed.


RESULTS
Allele frequencies of three tSNPs were significantly different between the positive and negative groups. They were rs696522 (odds ratio [OR] = 3.06, p = .0013), rs1381376 (OR = 3.16, p = .0008), and rs3778151 (OR = 3.12, p = .0004). Such association remains after adjustment for demographic covariates and for multiple testing. The subjects with heroin-induced positive responses on first use consumed more drugs than the negative group (Mann-Whitney U = 224.0, Wilcoxon W = 16334.0, p <or= .0001).


CONCLUSIONS
Self-reported positive responses on first use of heroin were found to be associated with OPRM1. The findings suggest that heroin-induced positive responses are likely associated with more heroin consumption.
Zhang
Dandan
D
MOE Key Laboratory of Contemporary Anthropology and Center for Evolutionary Biology, School of Life Sciences and Institutes of Biomedical Sciences, West Lafayette, Indiana, USA.
Shao
Chunhong
C
Shao
Minhua
M
Yan
Pengrong
P
Wang
Yi
Y
Liu
Yixiao
Y
Liu
Wenhong
W
Lin
Tong
T
Xie
Yuying
Y
Zhao
Yingnan
Y
Lu
Daru
D
Li
Yifeng
Y
Jin
Li
L
D000328:Adult; D002681:China; D005091:Exons / Q000235:genetics; D005260:Female; D005838:Genotype; D003932:Heroin / Q000494:pharmacology*; D006556:Heroin Dependence / Q000523:psychology; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D016015:Logistic Models; D008297:Male; D009294:Narcotics / Q000494:pharmacology*; D011110:Polymorphism, Genetic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D017450:Receptors, Opioid, mu / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D011795:Surveys and Questionnaires
D009294:Narcotics; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D003932:Heroin