| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Research Abstract |
Hypofunction of the N-methyl-D-aspartate (NMDA) type glutamate receptor-mediated neurotransmission has been hypothesized to underlie the pathophysiology of schizophrenia. In the presence of glutamte, NMDA receptor activity is modulated by glycine and D-serine. In this study, we examined the association of PAPST1 (3'-Phosphoadenosine 5'-Phosphosulfate Transporter 1) in schizophrenia and bipolar disorder, (1) because PAPST1 is the human ortholog of the rat dsm-1, D-serine modulator-1, which modulate the D-serine transport, and (2) because of the suggestion of a genetic overlap between affective disorders and schizophrenia. In the case-control study, three polymorphisms, rs 575034, rs 1875324 and rs 3832441, showed a significant association with bipolar disorder (allelic associations, p=.0074, p=.0075 and p=.0451, respectively). The test of genotype frequency of the SNP (rs3832441) remained significant even after Bonferroni correction (alpha=0.0071) for multiple testing. The haplotypes constructed from these three SNPs were also associated with the bipolar disorder. However, no association was found in family-based association analysis in Caucasian bipolar disorder trios. The present study suggests that SNPs in the PAPST1 may confer the genetic risk for bipolar disorder.
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