論文

査読有り
2018年1月1日

Association studies of WD repeat domain 3 and chitobiosyldiphosphodolichol beta-mannosyltransferase genes with schizophrenia in a Japanese population

PLoS ONE
  • Momoko Kobayashi
  • ,
  • Daisuke Jitoku
  • ,
  • Yoshimi Iwayama
  • ,
  • Naoki Yamamoto
  • ,
  • Tomoko Toyota
  • ,
  • Katsuaki Suzuki
  • ,
  • Mitsuru Kikuchi
  • ,
  • Tasuku Hashimoto
  • ,
  • Nobuhisa Kanahara
  • ,
  • Akeo Kurumaji
  • ,
  • Takeo Yoshikawa
  • ,
  • Toru Nishikawa

13
1
開始ページ
e0190991
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1371/journal.pone.0190991
出版者・発行元
Public Library of Science

Schizophrenia and schizophrenia-like symptoms induced by the dopamine agonists and N-methyl-D aspartate type glutamate receptor antagonists occur only after the adolescent period. Similarly, animal models of schizophrenia by these drugs are also induced after the critical period around postnatal week three. Based upon the development-dependent onsets of these psychotomimetic effects, by using a DNA microarray technique, we identified the WD repeat domain 3 (WDR3) and chitobiosyldiphosphodolichol beta-mannosyltransferase (ALG1) genes as novel candidates for schizophrenia-related molecules, whose mRNAs were up-regulated in the adult (postnatal week seven), but not in the infant (postnatal week one) rats by an indirect dopamine agonist, and phencyclidine, an antagonist of the NMDA receptor. WDR3 and other related proteins are the nuclear proteins presumably involved in various cellular activities, such as cell cycle progression, signal transduction, apoptosis, and gene regulation. ALG1 is presumed to be involved in the regulation of the protein N-glycosylation. To further elucidate the molecular pathophysiology of schizophrenia, we have evaluated the genetic association of WDR3 and ALG1 in schizophrenia. We examined 21 single nucleotide polymorphisms [SNPs
W1 (rs1812607)-W16 (rs6656360), A1 (rs8053916)-A10 (rs9673733)] from these genes using the Japanese case-control sample (1,808 schizophrenics and 2,170 matched controls). No significant genetic associations of these SNPs were identified. However, we detected a significant association of W4 (rs319471) in the female schizophrenics (allelic P = 0.003, genotypic P = 0.008). Based on a haplotype analysis, the observed haplotypes consisting of W4 (rs319471)–W5 (rs379058) also displayed a significant association in the female schizophrenics (P = 0.016). Even after correction for multiple testing, these associations remained significant. Our findings suggest that the WDR3 gene may likely be a sensitive factor in female patients with schizophrenia, and that modification of the WDR3 signaling pathway warrants further investigation as to the pathophysiology of schizophrenia.

リンク情報
DOI
https://doi.org/10.1371/journal.pone.0190991
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29309433
ID情報
  • DOI : 10.1371/journal.pone.0190991
  • ISSN : 1932-6203
  • PubMed ID : 29309433
  • SCOPUS ID : 85040322279

エクスポート
BibTeX RIS