Extended analyses support the association of a functional (GT)n polymorphism in the GRIN2A promoter with Japanese schizophrenia

Neurosci Lett. 2005 Apr 18;378(2):102-5. doi: 10.1016/j.neulet.2004.12.013. Epub 2005 Jan 6.

Abstract

Dysfunction of the N-methyl-D-aspartate (NMDA) type glutamate receptor has been proposed as a mechanism in the etiology of schizophrenia. Recently, we identified a variable (GT)n repeat in the promoter region of the NMDA NR2A subunit gene (GRIN2A), and showed its association with schizophrenia in a case-control study, together with a correlation between the length of the repeat and severity of chronic outcome. In this study, we extended our analyses, by increasing the number of case-control samples to a total of 672 schizophrenics and 686 controls, and excluded potential sample stratification effects. We confirmed the significant allelic association between the repeat polymorphism and disease (P = 0.011), and as in the previous study, we observed an over-representation of longer alleles in schizophrenia. These results suggest a probable genetic effect for the GRIN2A promoter (GT)n variation on the predisposition to schizophrenia in Japanese cohorts.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Chi-Square Distribution
  • Cohort Studies
  • Dinucleotide Repeats / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic*
  • Protein Subunits / genetics*
  • RNA, Messenger / biosynthesis
  • Receptors, N-Methyl-D-Aspartate / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Schizophrenia / genetics*

Substances

  • Protein Subunits
  • RNA, Messenger
  • Receptors, N-Methyl-D-Aspartate
  • N-methyl D-aspartate receptor subtype 2A