title: Genetic variant of prodynorphin gene is risk factor for methamphetamine dependence.
abstract: Previous studies have indicated that genetic factors substantially affect development of substance use disorders, including methamphetamine dependence. Prodynorphin (PDYN) is an opioid peptide precursor that yields dynorphins, endogenous kappa opioid-receptor agonists that play important roles in substance abuse. A physiologically active polymorphism of 1-4 repeats of a 68-bp element in the promoter region of the PDYN gene has been identified. We analyzed this polymorphism of the PDYN gene by a case-control association study in 143 patients with methamphetamine dependence and 209 healthy controls in the Japanese population. A 3- or 4-repeat allele in the PDYN gene promoter was found significantly more frequently in patients with methamphetamine dependence than in controls (chi(2)=9.45, p=0.0021). A 3- or 4-repeat allele in the PDYN gene promoter, which was shown to produce significantly higher transcription activity of the PDYN gene than a 1- or 2-repeat allele, is a genetic risk factor for development of methamphetamine dependence (odds ratio: 1.83, 95% CI=1.24-2.68).
authors.affiliation: Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nomura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ujike
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Kyohei
authors.initials: K
authors.lastname: Otani
authors.forename: Yukitaka
authors.initials: Y
authors.lastname: Morita
authors.forename: Makiko
authors.initials: M
authors.lastname: Kishimoto
authors.forename: Akiko
authors.initials: A
authors.lastname: Morio
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Harano
authors.forename: Toshiya
authors.initials: T
authors.lastname: Inada
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Yamada
authors.forename: Tokutaro
authors.initials: T
authors.lastname: Komiyama
authors.forename: Yoshimoto
authors.initials: Y
authors.lastname: Sekine
authors.forename: Nakao
authors.initials: N
authors.lastname: Iwata
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sora
authors.forename: Masaomi
authors.initials: M
authors.lastname: Iyo
authors.forename: Norio
authors.initials: N
authors.lastname: Ozaki
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Kuroda
mesh_terms: D000328:Adult; D019969:Amphetamine-Related Disorders / Q000235:genetics*; D016001:Confidence Intervals; D004745:Enkephalins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011498:Protein Precursors / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D012307:Risk Factors
chemical_list: D004745:Enkephalins; D011498:Protein Precursors; C033660:preproenkephalin