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Psychiatr Genet. 2005 Sep;15(3):215-21.

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

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Division of Disease Genes, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.



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.


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).


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 x 10(-6), Pcorrected=2.297 x 10(-5), P=2.825 x 10(-6), Pcorrected=5.933 x 10(-5) and P=2.02 x 10(-4), Pcorrected=4.242 x 10(-3), respectively). The same results were also obtained using the false discovery rate (BL) method at the threshold P value, 2.908 x 10(-3).


We conclude that the GRIN2D locus is a possible genomic region contributing to schizophrenia susceptibility in the Japanese population.

[Indexed for MEDLINE]

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