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Logo of behbrainBioMed CentralBiomed Central Web Sitesearchsubmit a manuscriptregisterthis articleBehavioral and Brain Functions : BBFJournal Front Page
Behav Brain Funct. 2008; 4: 37.
Published online Aug 15, 2008. doi:  10.1186/1744-9081-4-37
PMCID: PMC2542390
The Frizzled 3 gene is associated with methamphetamine psychosis in the Japanese population
Makiko Kishimoto,1 Hiroshi Ujike,corresponding author1,2 Yuko Okahisa,1 Tatsuya Kotaka,1 Manabu Takaki,1 Masafumi Kodama,1 Toshiya Inada,2,3 Mitsuhiko Yamada,2,4 Naohisa Uchimura,2,5 Nakao Iwata,2,6 Ichiro Sora,2,7 Masaomi Iyo,2,8 Norio Ozaki,2,9 and Shigetoshi Kuroda1
1Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
2JGIDA (Japanese Genetics Initiative for Drug Abuse), Japan
3Institute of Neuropsychiatry, Seiwa Hospital, Tokyo, Japan
4Department of Psychogeriatrics, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Japan
5Department of Neuropsychiatry, Kurume University Graduate School of Medicine, Kurume, Japan
6Department of Psychiatry, Fujita Health University School of Medicine, Houmei, Japan
7Department of Neuroscience, Division of Psychobiology, Tohoku University Graduate School of Medicine, Sendai, Japan
8Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan
9Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan
corresponding authorCorresponding author.
Makiko Kishimoto: makiko.kishimoto/at/; Hiroshi Ujike: hujike/at/; Yuko Okahisa: gmd15031/at/; Tatsuya Kotaka: tatsuya7kotaka7/at/; Manabu Takaki: manabuta/at/; Masafumi Kodama: m-kodama/at/; Toshiya Inada: han91010/at/; Mitsuhiko Yamada: mitsu/at/; Naohisa Uchimura: naohisa/at/; Nakao Iwata: nakao/at/; Ichiro Sora: isora/at/; Masaomi Iyo: iyom/at/; Norio Ozaki: ozaki-n/at/; Shigetoshi Kuroda: skuroda/at/
Received August 5, 2008; Accepted August 15, 2008.
Frizzled 3 (Fzd3) is a receptor required for the Wnt-signaling pathway, which has been implicated in the development of the central nervous system, including synaptogenesis and structural plasticity. We previously found a significant association between the FZD3 gene and susceptibility to schizophrenia, but subsequent studies showed inconsistent findings. To understand the roles of the FZD3 gene in psychotic disorders further, it should be useful to examine FZD3 in patients with methamphetamine psychosis because the clinical features of methamphetamine psychosis are similar to those of schizophrenia.
Six SNPs of FZD3, rs3757888 in the 3' flanking region, rs960914 in the intron 3, rs2241802, a synonymous SNP in the exon5, rs2323019 and rs352203 in the intron 5, and rs880481 in the intron 7, were selected based on the previous schizophrenic studies and analyzed in 188 patients with methamphetamine psychosis and 240 age- and gender-matched controls.
A case-control association analyses revealed that two kinds of FZD3 haplotypes showed strong associations with methamphetamine psychosis (p < 0.00001). Having the G-A-T-G or A-G-C-A haplotype of rs2241802-rs2323019-rs352203-rs880481 was a potent negative risk factor (odds ratios were 0.13 and 0.086, respectively) for methamphetamine psychosis.
Our present and previous findings indicate that genetic variants of the FZD3 gene affect susceptibility to two analogous but distinct dopamine-related psychoses, endogenous and substance-induced psychosis.
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