Identification of functional polymorphisms in the promoter region of the human PICK1 gene and their association with methamphetamine psychosis

Daisuke Matsuzawa, Kenji Hashimoto, Ryosuke Miyatake, Yukihiko Shirayama, Eiji Shimizu, Kazuhisa Maeda, Yoichi Suzuki, Yoichi Mashimo, Yoshimoto Sekine, Toshiya Inada, Norio Ozaki, Nakao Iwata, Mutsuo Harano, Tokutaro Komiyama, Mitsuhiko Yamada, Ichiro Sora, Hiroshi Ujike, Akira Hata, Akira Sawa, Masaomi Iyo

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31 Citations (Scopus)


Objective: Protein interacting with C-kinase-1 (PICK1) plays a role in the targeting and clustering of dopamine transporter, which is the primary target site for the abused drug methamphetamine. Based on the interaction of PICK1 with dopamine transporter, it is of particular interest to investigate the association between the PICK1 gene and methamphetamine abusers. Method: The authors studied the association between PICK1 gene polymorphisms and methamphetamine abusers in a Japanese group. Two hundred and eight methamphetamine abusers and 218 healthy comparison subjects were enrolled in the study. Furthermore, the authors also examined the effects of single nucleotide polymorphisms (SNPs) in the promoter and 5′-untranslated region on transcription levels of PICK1. Results: The authors identified four highly frequent SNPs, rs737622 (-332 C/G) and rs3026682 (-205 G/A) in the promoter region and rs713729 (T/A) in intron3 and rs2076369 (T/G) in intron4. Of these SNPs, rs713729 was significantly associated with methamphetamine abusers in general, and rs713729 and rs2076369 were significantly associated with those with spontaneous relapse of psychosis. Furthermore, haplotype analysis revealed that specific haplotypes of these SNPs were associated with methamphetamine abusers. A gene reporter assay revealed that the two SNPs in the promoter region significantly altered transcriptional activity. Conclusions: Our findings suggest that the PICK1 gene may be implicated in the susceptibility to spontaneous relapse of methamphetamine psychosis and that, as an intracellular adapter protein, PICK1 may play a role in the pathophysiology of methamphetamine psychosis.

Original languageEnglish
Pages (from-to)1105-1114
Number of pages10
JournalAmerican Journal of Psychiatry
Issue number7
Publication statusPublished - 2007 Jul
Externally publishedYes

ASJC Scopus subject areas

  • Psychiatry and Mental health


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