title: Identification of functional polymorphisms in the promoter region of the human PICK1 gene and their association with methamphetamine psychosis.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Matsuzawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Miyatake
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Shirayama
authors.forename: Eiji
authors.initials: E
authors.lastname: Shimizu
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Maeda
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Mashimo
authors.forename: Yoshimoto
authors.initials: Y
authors.lastname: Sekine
authors.forename: Toshiya
authors.initials: T
authors.lastname: Inada
authors.forename: Norio
authors.initials: N
authors.lastname: Ozaki
authors.forename: Nakao
authors.initials: N
authors.lastname: Iwata
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Harano
authors.forename: Tokutaro
authors.initials: T
authors.lastname: Komiyama
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Yamada
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sora
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ujike
authors.forename: Akira
authors.initials: A
authors.lastname: Hata
authors.forename: Akira
authors.initials: A
authors.lastname: Sawa
authors.forename: Masaomi
authors.initials: M
authors.lastname: Iyo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019969:Amphetamine-Related Disorders / Q000235:genetics* / Q000378:metabolism; D044466:Asian People / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D047668:Inteins / Q000235:genetics; D007564:Japan; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects / Q000378:metabolism; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011605:Psychoses, Substance-Induced / Q000175:diagnosis* / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D009687:Nuclear Proteins; C498297:PICk1 protein, human; D014157:Transcription Factors; D008694:Methamphetamine