Extended analyses support the association of a functional (GT)n polymorphism in the GRIN2A promoter with Japanese schizophrenia.
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.
Iwayama-Shigeno
Yoshimi
Y
Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama, Japan.
Yamada
Kazuo
K
Itokawa
Masanari
M
Toyota
Tomoko
T
Meerabux
Joanne M A
JM
Minabe
Yoshio
Y
Mori
Norio
N
Inada
Toshio
T
Yoshikawa
Takeo
T
D000328:Adult; D016009:Chi-Square Distribution; D015331:Cohort Studies; D018900:Dinucleotide Repeats / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D021122:Protein Subunits / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012559:Schizophrenia / Q000235:genetics*
D021122:Protein Subunits; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate