| 1 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2009 Apr 33: 511-8 |
|---|---|
| PMID | 19223009 |
| Title | Association analysis of glycine- and serine-related genes in a Japanese population of patients with schizophrenia. |
| Abstract | Differences in the levels of the glutamate-related amino acids glycine and serine in brain/plasma betweenschizophrenicpatients and normal subjects and changes in the plasma concentrations of these amino acids according to the clinical course have been reported. It has been hypothesized that glycine and serine metabolism may be altered inschizophrenia. In fact, some genes related to the metabolism of these amino acids have been suggested to be candidate genes forschizophrenia. Thus, we performed a genomic case-control analysis of amino acid metabolism-related genes in Japanese patients withschizophrenia. Case-control genetic association analysis of PHGDH,SHMT1, SRR, and DAO was performed. In addition, the effect of the various genotypes resulting from these four genes on changes in plasma amino acid levels inschizophreniawas assessed. The genetic case-control analysis showed that no individual single-nucleotide polymorphism (SNP) in any of the four genes was associated withschizophrenia; only the two (rs3918347-rs4964770, P=0.0009) and three (rs3825251-rs3918347-rs4964770, P=0.002) SNP-based haplotype analysis of the DAO gene showed an association withschizophreniaeven after correction for multiple testing. None of the genotypes studied was associated with changes in the plasma glycine and l- and d-serine levels during theschizophrenicclinical course. The DAO gene may be a susceptibility locus forschizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 2 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2009 Apr 33: 511-8 |
| PMID | 19223009 |
| Title | Association analysis of glycine- and serine-related genes in a Japanese population of patients with schizophrenia. |
| Abstract | Differences in the levels of the glutamate-related amino acids glycine and serine in brain/plasma betweenschizophrenicpatients and normal subjects and changes in the plasma concentrations of these amino acids according to the clinical course have been reported. It has been hypothesized that glycine and serine metabolism may be altered inschizophrenia. In fact, some genes related to the metabolism of these amino acids have been suggested to be candidate genes forschizophrenia. Thus, we performed a genomic case-control analysis of amino acid metabolism-related genes in Japanese patients withschizophrenia. Case-control genetic association analysis of PHGDH,SHMT1, SRR, and DAO was performed. In addition, the effect of the various genotypes resulting from these four genes on changes in plasma amino acid levels inschizophreniawas assessed. The genetic case-control analysis showed that no individual single-nucleotide polymorphism (SNP) in any of the four genes was associated withschizophrenia; only the two (rs3918347-rs4964770, P=0.0009) and three (rs3825251-rs3918347-rs4964770, P=0.002) SNP-based haplotype analysis of the DAO gene showed an association withschizophreniaeven after correction for multiple testing. None of the genotypes studied was associated with changes in the plasma glycine and l- and d-serine levels during theschizophrenicclinical course. The DAO gene may be a susceptibility locus forschizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 3 | Nihon Shinkei Seishin Yakurigaku Zasshi 2010 Nov 30: 197-200 |
| PMID | 21226315 |
| Title | [Analysis of mouse strain-dependent prepulse inhibition points to a role for Shmt1 (SHMT1) in mice and in schizophrenia]. |
| Abstract | Deficits in prepulse inhibition (PPI) are thought to be a biological trait of mental illnesses, includingschizophrenia. It is known that the N-methyl-D-aspartate type glutamate (NMDA) receptor function affects PPI integrity and D-serine and glycine are typical endogenous co-agonists for the receptor. In parallel, we re-visited our prior quantitative trait loci (QTL) analysis study that examined C57BL/6 (B6) mice with high PPI and C3H/He (C3) with low PPI, and noticed that the genes encoding enzymes responsible for the productions of D-serine (serine racemase: Srr) and glycine (serine hydroxymethyltransferase 1:SHMT1) map to the chromosome 11 QTL. Therefore, we set out to examine whether brain interstitial fluid (ISF) levels of the two amino acids are different between the two mouse strains, using in vivo microdialysis. Recovery of D-serine and glycine from the dialysate of the frontal cortex was higher in B6 mice, which performed better in PPI, compared to C3 mice. Next, we analyzed the two genes, Srr andSHMT1. We then identified promoter polymorphisms inSHMT1B6引起较低的转录活动compared to C3 mice. Human studies revealed higher expression levels ofSHMT1in the frontal cortex of postmortem brains fromschizophrenics compared to controls, but no changes in SRR levels. In addition, genetic analysis detected a nominal association betweenSHMT1andschizophrenia. These results suggest thatSHMT1(SHMT1) is one of the genetic components regulating PPI in mice and is relevant toschizophreniasusceptibility in humans. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 4 | Nihon Shinkei Seishin Yakurigaku Zasshi 2010 Nov 30: 197-200 |
| PMID | 21226315 |
| Title | [Analysis of mouse strain-dependent prepulse inhibition points to a role for Shmt1 (SHMT1) in mice and in schizophrenia]. |
| Abstract | Deficits in prepulse inhibition (PPI) are thought to be a biological trait of mental illnesses, includingschizophrenia. It is known that the N-methyl-D-aspartate type glutamate (NMDA) receptor function affects PPI integrity and D-serine and glycine are typical endogenous co-agonists for the receptor. In parallel, we re-visited our prior quantitative trait loci (QTL) analysis study that examined C57BL/6 (B6) mice with high PPI and C3H/He (C3) with low PPI, and noticed that the genes encoding enzymes responsible for the productions of D-serine (serine racemase: Srr) and glycine (serine hydroxymethyltransferase 1:SHMT1) map to the chromosome 11 QTL. Therefore, we set out to examine whether brain interstitial fluid (ISF) levels of the two amino acids are different between the two mouse strains, using in vivo microdialysis. Recovery of D-serine and glycine from the dialysate of the frontal cortex was higher in B6 mice, which performed better in PPI, compared to C3 mice. Next, we analyzed the two genes, Srr andSHMT1. We then identified promoter polymorphisms inSHMT1B6引起较低的转录活动compared to C3 mice. Human studies revealed higher expression levels ofSHMT1in the frontal cortex of postmortem brains fromschizophrenics compared to controls, but no changes in SRR levels. In addition, genetic analysis detected a nominal association betweenSHMT1andschizophrenia. These results suggest thatSHMT1(SHMT1) is one of the genetic components regulating PPI in mice and is relevant toschizophreniasusceptibility in humans. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 5 | J. Neurochem. 2010 Dec 115: 1374-85 |
| PMID | 20977478 |
| Title | Analysis of strain-dependent prepulse inhibition points to a role for Shmt1 (SHMT1) in mice and in schizophrenia. |
| Abstract | Deficits in prepulse inhibition (PPI) are known in mental illnesses, includingschizophrenia. NMDA receptor function affects PPI integrity and D-serine and glycine are endogenous co-agonists for the receptor. Our previous quantitative trait loci analysis using C57BL/6 (B6) mice with better PPI performance and C3H/He (C3) with lower PPI score, shows that genes for both D-serine synthesizing enzyme and enzyme for reversible conversion between glycine and L-serine (Srr andSHMT1, respectively) are located in the same PPI-quantitative trait loci peak. Therefore, we set out to determine which gene is likely to explain the PPI difference and whether the gene is potentially relevant toschizophrenia. We first examined brain interstitial fluid levels of the two amino acids using microdialysis. Recovery of D-serine and glycine from the dialysate was higher in B6, compared to C3. Next, we analyzed expression levels and genetic polymorphisms of the two genes. There were promoter polymorphisms inSHMT1, which elicit lower transcriptional activity in B6 compared to C3 conforming to the results of brain expression levels, but no functional genetic variants in Srr. Finally, we evaluated expression levels of the two genes in the postmortem brains ofschizophreniaand genetic associations with the disease. TheSHMT1levels were higher inschizophrenic大脑控制相比,但没有变化in SRR levels. We detected a nominal association betweenSHMT1andschizophrenia. These results suggest thatSHMT1(SHMT1), but not Srr, is likely to be one of the genetic components regulating PPI in mice and possibly relevant toschizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 6 | J. Neurochem. 2010 Dec 115: 1374-85 |
| PMID | 20977478 |
| Title | Analysis of strain-dependent prepulse inhibition points to a role for Shmt1 (SHMT1) in mice and in schizophrenia. |
| Abstract | Deficits in prepulse inhibition (PPI) are known in mental illnesses, includingschizophrenia. NMDA receptor function affects PPI integrity and D-serine and glycine are endogenous co-agonists for the receptor. Our previous quantitative trait loci analysis using C57BL/6 (B6) mice with better PPI performance and C3H/He (C3) with lower PPI score, shows that genes for both D-serine synthesizing enzyme and enzyme for reversible conversion between glycine and L-serine (Srr andSHMT1, respectively) are located in the same PPI-quantitative trait loci peak. Therefore, we set out to determine which gene is likely to explain the PPI difference and whether the gene is potentially relevant toschizophrenia. We first examined brain interstitial fluid levels of the two amino acids using microdialysis. Recovery of D-serine and glycine from the dialysate was higher in B6, compared to C3. Next, we analyzed expression levels and genetic polymorphisms of the two genes. There were promoter polymorphisms inSHMT1, which elicit lower transcriptional activity in B6 compared to C3 conforming to the results of brain expression levels, but no functional genetic variants in Srr. Finally, we evaluated expression levels of the two genes in the postmortem brains ofschizophreniaand genetic associations with the disease. TheSHMT1levels were higher inschizophrenic大脑控制相比,但没有变化in SRR levels. We detected a nominal association betweenSHMT1andschizophrenia. These results suggest thatSHMT1(SHMT1), but not Srr, is likely to be one of the genetic components regulating PPI in mice and possibly relevant toschizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |