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Human Kappa opioid receptor gene (OPRK1) polymorphism is associated with opiate addiction
Author(s) -
Gerra G.,
Leonardi C.,
Cortese E.,
D'Amore A.,
Lucchini A.,
Strepparola G.,
Serio G.,
Farina G.,
Magnelli F.,
Zaimovic A.,
Mancini A.,
Turci M.,
Manfredini M.,
Donnini C.
Publication year - 2007
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.30510
Subject(s) - κ opioid receptor , single nucleotide polymorphism , opiate , heroin , addiction , snp , harm avoidance , opioid , kappa , substance dependence , psychology , medicine , methamphetamine , genetics , receptor , psychiatry , gene , biology , personality , genotype , drug , big five personality traits , social psychology , linguistics , philosophy
Abstract Variants of the opioid receptors are the obvious candidates underlying addiction. The kappa opioid receptor (KOR) system seems to play a role in stress responsivity, opiate withdrawal and responses to psycho‐stimulants, inhibiting mesolimbic dopamine. KOR gene polymorphisms have been reported to contribute to predisposition to voluntary alcohol‐drinking behavior in experimental animals. In humans, the 36G > T single nucleotide polymorphism (SNP) on KOR gene, that was recently identified, has been found associate with substance dependence, with inconclusive findings. In the present study, 106 heroin addicts (West European, Caucasians) and 70 healthy control subjects matched for race and gender, with no history of substance use disorder, have been genotyped. The frequency of KOR 36G > T SNP was significantly higher among heroin‐dependent individuals compared with control subjects (Fisher's exact = 0.044; Pearson χ 2 = 4.2734, P = 0.039; likelihood ratio χ 2 tests = 4.6156, P = 0.032). Although KOR silent polymorphisms may apparently have no consequences on mRNA transcription, post‐transcriptional mechanisms, such as mRNA stability, translation efficiency, and regulability may impair the function of kappa receptors system, with increased risk for substance use disorders. In specific, the neurobiological changes induced by mu‐kappa opioid imbalance could underlie vulnerable personality traits and risk behavior. © 2007 Wiley‐Liss, Inc.