title: A decrease in protein level and a missense polymorphism of KIF17 are associated with schizophrenia.
abstract: It has been shown that the dysfunction of N-methyl-d-asparate (NMDA) receptors-mediated neurotransmission plays a role in the pathophysiology of schizophrenia. Especially, GluN2B, a subunit of NMDA receptors, associated trafficking complex is altered in the prefrontal cortex of schizophrenia. The kinesin superfamily motor protein 17 (KIF17) is known as a transporter of NR2B.Previous studies showed that a structural variant of KIF17 gene is associated with a schizophrenic phenotype. Therefore, here we investigated KIF17 levels in postmortem prefrontal cortex in schizophrenia and the association of a missense polymorphism (Ile341Val) in KIF17 with schizophrenia. The protein expression of KIF17 in schizophrenic postmortem brains was significantly lower than that in controls. Next, the association of missense polymorphisms (rs631375, rs13375609, rs522496 and rs2296225) of KIF17 gene in 567 schizophrenia and 710 healthy subjects was examined. Both genotypic distribution and allelic frequency of rs2296225 polymorphism were significantly different between the chronic schizophrenia subjects and controls. However, our findings described above were not replicated with the independent subjects (555 schizophrenia and 814 healthy controls). Furthermore, the two alleles of rs2296225 polymorphism did not affect the mRNA expression of KIF17. These results suggest that the dysfunction of KIF17 might be involved in the pathophysiology of schizophrenia.
authors.affiliation: Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Japan0.
authors.forename: Woraphat
authors.initials: W
authors.lastname: Ratta-Apha
authors.affiliation: Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Japan0.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Mouri
authors.affiliation: Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Japan0.
authors.forename: Shuken
authors.initials: S
authors.lastname: Boku
authors.affiliation: Department of Psychiatry, Tsukuba University Graduate School of Medicine, Tsukuba, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ishiguro
authors.affiliation: Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Japan0.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okazaki
authors.affiliation: Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Japan0.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Otsuka
authors.affiliation: Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Japan0.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sora
authors.affiliation: Department of Psychiatry, Tsukuba University Graduate School of Medicine, Tsukuba, Japan.
authors.forename: Tadao
authors.initials: T
authors.lastname: Arinami
authors.affiliation: Department of Neuropsychiatry, Kinki University School of Medicine, Osaka, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Shirakawa
authors.affiliation: Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Japan0. Electronic address: hishipon@med.kobe-u.ac.jp.
authors.forename: Akitoyo
authors.initials: A
authors.lastname: Hishimoto
mesh_terms: D000328:Adult; D001344:Autopsy; D005260:Female; D005787:Gene Frequency; D064368:Healthy Volunteers; D006801:Humans; D016547:Kinesins / Q000032:analysis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D017397:Prefrontal Cortex / Q000378:metabolism*; D021381:Protein Transport / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology
chemical_list: C485813:KIF17 protein, human; D012333:RNA, Messenger; D016547:Kinesins
keywords: KIF17; Postmortem brain; Schizophrenia; Single nucleotide polymorphism