title: Association between cerebrospinal fluid dopamine concentrations and catechol-O-methyltransferase gene polymorphisms in forensic autopsy cases of methamphetamine abusers.
abstract: Methamphetamine (MA) is an illicit psychostimulant that stimulates the release of catecholamines from sympathetic nerve terminals and is widely abused worldwide. Since catechol-O-methyltransferase (COMT) metabolizes catecholamines and mediates adrenergic, noradrenergic, and dopaminergic signaling responses, we investigated the effects of the COMT polymorphisms rs4633 and rs4680 on cerebrospinal fluid (CSF) catecholamine concentrations in autopsies of subjects who died of drug intoxication. 28 MA abusers and 22 fatal psychotropic drug intoxication cases were evaluated. No correlations were identified between rs4633 or rs4680 polymorphisms and CSF concentrations of adrenaline (Adr), noradrenaline (Nad), or dopamine (DA) in fatal psychotropic cases. However, among MA abusers, DA concentrations in the CSF were significantly higher in those with the T allele (CT and TT) of rs4633 than in CC genotype carriers (p=0.004). Moreover, among MA abusers, DA concentrations were significantly higher in those with the A allele (GA and AA) of rs4680 than in GG genotype carriers (p=0.017). In subsequent haplotype analyses of MA abusers, a strong correlation was identified between two COMT haplotypes and CSF DA concentrations (p=0.002). However, the CSF concentrations of Adr and Nad were not associated with COMT genotypes or haplotypes. The present results indicate that rs4633 and rs4680 polymorphisms influence CSF DA concentrations and MA toxicity in MA abusers.
authors.affiliation: Department of Forensic Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan. Electronic address: miyoshi@fukuoka-u.ac.jp.
authors.forename: Aya
authors.initials: A
authors.lastname: Matsusue
authors.affiliation: Department of Legal Medicine, Osaka City University Medical School, Asahi-machi 1-4-3, Abeno, Osaka 545-8585, Japan.
authors.forename: Takaki
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Department of Legal Medicine, Osaka City University Medical School, Asahi-machi 1-4-3, Abeno, Osaka 545-8585, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Michiue
authors.affiliation: Department of Forensic Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
authors.forename: Brian
authors.initials: B
authors.lastname: Waters
authors.affiliation: Department of Forensic Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Hara
authors.affiliation: Department of Forensic Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kashiwagi
authors.affiliation: Department of Forensic Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
authors.forename: Mio
authors.initials: M
authors.lastname: Takayama
authors.affiliation: Department of Forensic Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
authors.forename: Natsuki
authors.initials: N
authors.lastname: Ikematsu
authors.affiliation: Department of Forensic Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Kubo
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D019969:Amphetamine-Related Disorders; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D004298:Dopamine / Q000134:cerebrospinal fluid*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D055815:Young Adult
chemical_list: D008694:Methamphetamine; D002394:Catechol O-Methyltransferase; D004298:Dopamine
keywords: Catechol-O-methyltransferase; Cerebrospinal fluid; Dopamine; Methamphetamine; Polymorphism