A missense mutation in the ITGA8 gene, a cell adhesion molecule gene, is associated with schizophrenia in Japanese female patients

Irwan Supriyanto, Yuichiro Watanabe, Kentaro Mouri, Kyoichi Shiroiwa, Woraphat Ratta-Apha, Masakuni Yoshida, Genki Tamiya, Toru Sasada, Noriomi Eguchi, Kenji Okazaki, Osamu Shirakawa, Toshiyuki Someya, Akitoyo Hishimoto

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Background: Cell adhesion molecules (CAMs) play pivotal role in the development of the central nervous system (CNS) and have also been reported to play role in the pathophysiology of schizophrenia. Missense mutations in the CAMs genes might alter the binding of their ligands, increasing the vulnerability to develop schizophrenia. Methods: We selected 15 missense mutations in the CAMs genes of the CNS reported in the Kyoto Encyclopedia of Genes and Genomes (KEGG) and examined the association between these mutations and schizophrenia in 278 patients and 284 control subjects (first batch). We also genotyped the positive single nucleotide polymorphisms (SNPs) in 567 patients and 710 control subjects (second batch) and in 635 patients and 639 control subjects (replication samples). Results: Genotypic and allelic distributions of rs2298033 in the ITGA8 gene between the schizophrenia and control groups were significantly different in the first batch (p = 0.005 and 0.007, respectively). Gender-based analysis revealed that the allelic and genotypic distributions of rs2298033 in the ITGA8 were significantly different between the schizophrenia and control groups among females in both batches (p = 0.010, 0.011 and 0.0086, 0.010, respectively) but not among males. Combine analysis of rs2298033 with the replication samples revealed a more significant differences (p = 0.0032; 0.0035 in the overall subjects and p = 0.0024; 0.0025 in the female subjects, respectively). The significant differences for rs2802808 of the NFASC gene were only observed in the female subgroup of the first batch. Conclusion: These results suggest that the ITGA8 gene might have gender-specific roles in the development of schizophrenia. Further replication and functional studies are required to confirm these findings.

Original languageEnglish
Pages (from-to)347-352
Number of pages6
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume40
Issue number1
DOIs
Publication statusPublished - 2013 Jan 10
Externally publishedYes

Keywords

  • Association study
  • Cell adhesion molecules
  • Integrin
  • Neurofascin
  • Schizophrenia

ASJC Scopus subject areas

  • Pharmacology
  • Biological Psychiatry

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