A decrease in protein level and a missense polymorphism of KIF17 are associated with schizophrenia. Issue 2 (15th December 2015)

• Record Type: Journal Article
• Authors: Ratta-apha, Woraphat; Mouri, Kentaro; Boku, Shuken; Ishiguro, Hiroki; Okazaki, Satoshi; Otsuka, Ikuo; Sora, Ichiro; Arinami, Tadao; Shirakawa, Osamu; Hishimoto, Akitoyo
• Is Part Of: Psychiatry research. Voume 230:Issue 2(2015)
• Page Start: 424
• Page End: 429
• Publication Date: 2015-12-15
• Subjects: KIF17 kinesin superfamily motor protein 17 -- NMDA N-methyl-d-asparate -- GluN2B NMDA receptor subunit 2B -- SNP single nucleotide polymorphism -- DSM-IV diagnostic and statistical manual of mental disorders 4th edition; KIF17 -- Single nucleotide polymorphism -- Schizophrenia -- Postmortem brain; Psychiatry -- Periodicals; Psychiatry -- periodicals; Psychiatrie -- Périodiques; 616.89
• DOI: 10.1016/j.psychres.2015.09.031
• Languages: English
• ISSNs: 0165-1781

Abstract

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. Highlights: We examined KIF17 expression in postmortem prefrontal cortex. KIF17 expression in schizophrenia was significantly less than that in controls. Two alleles of Ile341Val polymorphism did not affect the mRNA expression of KIF17. We examined the association of missense polymorphism in KIF17 with schizophrenia. Previous positive association of Ile341Val was not replicated with independent set.