Identification of single-nucleotide polymorphisms in the human N-methyl-D-aspartate receptor subunit NR2D gene, GRIN2D, and association study with schizophrenia

Chieko Makino, Hiroki Shibata, Hideaki Ninomiya, Nobutada Tashiro, Yasuyuki Fukumaki

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    25 Citations (Scopus)

    Abstract

    Objectives: The glutamatergic dysfunction is one of the main hypotheses for the pathophysiology of schizophrenia. N-methyl-D-aspartate receptors are of major interest because phencyclidine, a non-competitive antagonist of N-methyl-D-aspartate receptors, produces a schizophrenia-like psychosis. Therefore, the genes encoding N-methyl-D-aspartate receptor subunits are strong candidates for schizophrenia susceptibility genes. We focused on the N-methyl-D-aspartate receptor subunit NR2D gene in the case-control study of schizophrenia. Methods: We screened for polymorphisms in exons, exon-intron boundaries and the 5′ upstream region of GRIN2D by direct sequencing in 32 Japanese patients. Out of the total 13 single-nucleotide polymorphisms identified, we genotyped 200-201 Japanese patients and 219-221 controls for nine common single-nucleotide polymorphisms (minor allele frequency over 0.05). Results: None of the nine single-nucleotide polymorphisms showed significant differences in genotype and allele frequencies between cases and controls. We observed significant associations of pairwise haplotypes in three combinations of four single-nucleotide polymorphisms, INT10SNP-EX13SNP2, EX13SNP2-EX13SNP3 and EX6SNP-EX13SNP2, with the disease even after the Bonferroni correction (P=1.094 × 10-6, Pcorrected=2.297 × 10 -5, P=2.825 × 10-6, Pcorrected=5.933 × 10-5 and P=2.02 × 10-4, P corrected=4.242 × 10-3, respectively). The same results were also obtained using the false discovery rate (BL) method at the threshold P value, 2.908 × 10-3. Conclusions: We conclude that the GRIN2D locus is a possible genomic region contributing to schizophrenia susceptibility in the Japanese population.

    Original languageEnglish
    Pages (from-to)215-221
    Number of pages7
    JournalPsychiatric Genetics
    Volume15
    Issue number3
    DOIs
    Publication statusPublished - Sept 2005

    All Science Journal Classification (ASJC) codes

    • Genetics
    • Genetics(clinical)
    • Psychiatry and Mental health
    • Biological Psychiatry

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