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Tatsuyuki Muratake

Publications and source records attributed to Tatsuyuki Muratake.

14 recordsLinked to original sources
PubMed2007

Synergistic association of mitochondrial uncoupling protein (UCP) genes with schizophrenia.

Many studies suggest that mitochondrial dysfunction is involved in the pathophysiology of schizophrenia. We performed a case-control study using tag SNPs in the mitochondrial uncoupling protein genes, UCP2, UCP4, and BMCP1/UCP5, to investigate their association with schizophrenia. These neuronal UCPs are expressed in various brain tissues and may exert a neuroprotective effect against increased oxidative stress. We found modest associations between schizophrenia and the four tag SNPs, rs660339 (odds ratio (OR) = 1.330; P = 0.0043) and rs649446 (OR = 0.739; P = 0.0069) in UCP2, and rs10807344 (OR = 0.622; P = 0.0029) and rs2270450 (OR = 0.704; P = 0.0043) in UCP4, all of which were statistically significant even after correcting for multiple comparisons. Moreover, we found a statistically significant synergistic interaction between UCP2 and UCP4 by using the multifactor dimensionality reduction (MDR) method. The synergistic interaction was also confirmed by the logistic regression analysis, where the maximal OR was obtained when the risk alleles at rs660339 and rs10807344 were simultaneously homozygous. Individuals possessing homozygous risk alleles at these two loci have a 7.6-fold risk of developing schizophrenia compared with those of minimal OR. Our findings suggest that UCP2 and UCP4 have a modest but important involvement in the genetic etiology of schizophrenia. This is the first report of the association between schizophrenia and neuronal UCPs.

Alleles↗
PubMed2006

No association between the brain-derived neurotrophic factor gene and schizophrenia in a Japanese population.

Brain-derived neurotrophic factor (BDNF) plays important roles in the survival, maintenance and growth of neurons. Several studies have indicated that BDNF is likely to be related to the pathogenesis of schizophrenia. Recent genetic analyses have revealed that BDNF gene polymorphisms are associated with schizophrenia, although contradictory negative findings have also been reported. To assess whether three BDNF gene polymorphisms (rs988748, C132T and rs6265) could be implicated in vulnerability to schizophrenia, we conducted a case-control association analysis (349 patients and 423 controls) in Japanese subjects. We found no association between these BDNF gene polymorphisms and schizophrenia using both single-marker and haplotype analyses. The results of the present study suggest that these three BDNF gene polymorphisms do not play major roles in conferring susceptibility to schizophrenia in a Japanese population. However, further studies assessing the associations between these BDNF gene polymorphisms and schizophrenia should be performed in several other ethnic populations.

Adult↗
PubMed2006

Association study of a functional promoter polymorphism of the X-box binding protein 1 gene in Japanese patients with schizophrenia.

The functional promoter polymorphism -116C/G of the X-box binding protein 1 (XBP1) gene was found to be associated with schizophrenia in Han Chinese and Japanese subjects, although contradictive negative findings were also reported in European populations. To confirm this association in a Japanese population, the authors conducted a case-control association study. There was no significant difference in both genotype and allele frequencies between the patients and control subjects, suggesting that the XBP1 -116C/G polymorphism might not confer increased susceptibility for schizophrenia in a Japanese population. However, further studies using a larger sample with detailed clinical data should be performed in several populations.

Adult↗
PubMed2005

Supportive evidence for neuregulin 1 as a susceptibility gene for schizophrenia in a Japanese population.

Schizophrenia is a complex genetic disorder and affects approximately 1% of the population worldwide. Recently, Stefansson et al. identified neuregulin 1 (NRG1) on 8p12 as a susceptibility gene for schizophrenia in the Icelandic population. It was reported that the at-risk haplotype ("Hapice") constructed from five SNPs and two microsatellite markers was found to be over-represented in patients with schizophrenia compared to controls. Since then several independent studies have supported the association of NRG1 with schizophrenia. We performed a case-control association study using the four SNPs in a Japanese sample. We genotyped three SNPs (SNP8NRG221533, SNP8NRG241930, and SNP8NRG243177) from Stefansson et al. and one SNP (rs1081062) located in intron 1 of NRG1. There were no significant differences in allele frequencies for each SNP between cases and controls, however, homozygotes of minor alleles in SNP8NRG241930, SNP8NRG243177, and rs1081062 were associated with an increased risk of schizophrenia (P=0.025, OR=4.14; P=0.041, OR=1.43; and P=0.0023, OR=3.06, respectively). Furthermore, the haplotype constructed from four SNPs shows a significant association with schizophrenia (permutation P=0.026). Our data support the hypothesis that NRG1 gene is a susceptibility gene for schizophrenia.

Adult↗
PubMed2005

Genomewide high-density SNP linkage analysis of 236 Japanese families supports the existence of schizophrenia susceptibility loci on chromosomes 1p, 14q, and 20p.

The Japanese Schizophrenia Sib-Pair Linkage Group (JSSLG) is a multisite collaborative study group that was organized to create a national resource for affected sib pair (ASP) studies of schizophrenia in Japan. We used a high-density single-nucleotide-polymorphism (SNP) genotyping assay, the Illumina BeadArray linkage mapping panel (version 4) comprising 5,861 SNPs, to perform a genomewide linkage analysis of JSSLG samples comprising 236 Japanese families with 268 nonindependent ASPs with schizophrenia. All subjects were Japanese. Among these families, 122 families comprised the same subjects analyzed with short tandem repeat markers. All the probands and their siblings, with the exception of seven siblings with schizoaffective disorder, had schizophrenia. After excluding SNPs with high linkage disequilibrium, we found significant evidence of linkage of schizophrenia to chromosome 1p21.2-1p13.2 (LOD=3.39) and suggestive evidence of linkage to 14q11.2 (LOD=2.87), 14q11.2-q13.2 (LOD=2.33), and 20p12.1-p11.2 (LOD=2.33). Although linkage to these regions has received little attention, these regions are included in or partially overlap the 10 regions reported by Lewis et al. that passed the two aggregate criteria of a meta-analysis. Results of the present study--which, to our knowledge, is the first genomewide analysis of schizophrenia in ASPs of a single Asian ethnicity that is comparable to the analyses done of ASPs of European descent--indicate the existence of schizophrenia susceptibility loci that are common to different ethnic groups but that likely have different ethnicity-specific effects.

Chromosomes, Human, Pair 1↗
PubMed2005

No association of EGF polymorphism with schizophrenia in a Japanese population.

Epidermal growth factor (EGF) signal regulates the development of dopaminergic neurons and monoamine metabolism. It is suggested that EGF protein levels are decreased in the brain and blood of patients with schizophrenia. A recent study has reported that a polymorphism in EGF gene (rs4444903) is associated with schizophrenia in Finnish men. To confirm this association for another population in larger samples, we conducted a case-control association study on a Japanese population (337 cases and 421 controls). No significant difference was observed in both the allelic and genotype distribution between cases and controls in women, men and total samples. Our results suggest that the polymorphism in EGF gene might not confer increased susceptibility for schizophrenia in a Japanese population.

Adult↗
PubMed2005

Linkage disequilibrium in aquaporin 4 gene and association study with schizophrenia.

Aquaporin 4 (AQP4) has an important role in water homeostasis of human brain and a dysfunction of AQP4 could induce pathological conditions in neuronal activity. Several genome scan studies for schizophrenia found a suggestive linkage on 18q, where human AQP4 (18q11.2-12.1) is located nearby. A case-control study was performed which comprised 261 schizophrenia subjects and 278 controls from the Japanese population with four SNP markers. We found strong linkage disequilibrium (LD) and an LD block in the AQP4 gene but found no association between AQP4 and schizophrenia, both single SNP and haplotype analyses. The present study shows that AQP4 is not directly associated with schizophrenia in these Japanese patients.

Adult↗
PubMed2004

Genetic and expression analyses of FZD3 in schizophrenia.

BACKGROUND: Wnt signaling plays important roles in neurodevelopmental processes. Frizzled is a receptor of Wnt protein, and the Frizzled 3 (FZD3) gene was recently reported to be associated with schizophrenia. Our study attempted to confirm associations between FZD3 and schizophrenia in Japanese family and case-control samples. METHODS: Genetic associations were evaluated using family-based transmission tests (212 families, 643 subjects) and case--control analysis (540 schizophrenia patients, 540 control sample). Six single nucleotide polymorphisms (SNPs) on the FZD3 locus were genotyped, and levels of FZD3 mRNA expression in postmortem brains were examined. RESULTS: Neither family- nor population-based studies supported associations between FZD3 and schizophrenia. FZD3 expression was unaltered in schizophrenic brains. CONCLUSIONS: Although two prior studies have reported associations using limited numbers of SNPs on FZD3, our intensive study failed to support any major contribution of FZD3 to schizophrenia susceptibility.

Adult↗
PubMed2004

Transmission disequilibrium test and haplotype analysis of the NOTCH4 gene in Japanese patients with schizophrenia.

A recent study reported that the NOTCH4 gene was highly associated with schizophrenia in the British population. To confirm this association for another population, a case-control study was conducted and a transmission disequilibrium test (TDT) analysis was performed on a group of Japanese subjects (235 pairs of schizophrenia patients and controls, and 78 trios consisting of probands and their parents) using two single nucleotide polymorphisms and three microsatellite markers for the NOTCH4 gene. Haplotype analysis was also studied in case-control and family based data sets. In all markers except for (CTG)n (P = 0.012, before correction for multiple testing), no differences were found in the case-control study. The TDT analysis also revealed only a weak transmission disequilibrium in (TTAT)n (genotype-wise P = 0.012). The finding of the present study could not support the original findings that the NOTCH4 gene itself is associated with susceptibility to schizophrenia.

Adult↗
PubMed2003

A psychometrically derived impulsive trait related to a polymorphism in the serotonin transporter gene-linked polymorphic region (5-HTTLPR) in a Japanese nonclinical population: assessment by the Barratt impulsiveness scale (BIS).

Although a number of studies have shown that human impulsive traits are associated with indices of central serotonin function, few researchers have investigated the relationship between a polymorphism in the serotonin transporter gene-linked region (5-HTTLPR) and a psychometrically derived impulsive trait. We determined the 5-HTTLPR polymorphism in 123 employed Japanese male adults using the polymerase chain reaction. The distribution of allelic frequency was determined and also investigated the relationship of the 5-HTTLPR polymorphism to a impulsive trait as measured by the Barratt Impulsiveness Scale, 11th version (BIS-11). The distribution of allelic frequency was found to be almost identical to that previously reported in Japanese (the frequency for the long (L)/L, L/short (S), and S/S genotypes was: 3, 28, and 68%, respectively). In a comparison between the genotype groups, the S/S genotype group significantly higher scored for the total BIS-11 and the subscale attentional impulsiveness than the L/S + L/L genotype group. These findings suggest that individuals with a homozygous S-allele may be more impulsive than those with the other genotype.

Carrier Proteins↗
PubMed2003

Effects of concomitant fluvoxamine on the metabolism of alprazolam in Japanese psychiatric patients: interaction with CYP2C19 mutated alleles.

OBJECTIVES: Administration of fluvoxamine (FLV) with concomitant benzodiazepines is common in clinical situations. We studied the effects of the coadministration of FLV on plasma concentrations of alprazolam (ALP). We also studied the effects of CYP2C19(*)2 or CYP2C19(*)3 on these drug interactions. METHODS: The subjects were 23 Japanese outpatients all concomitantly treated with FLV either before or after monotherapy with ALP. We measured the plasma concentrations of ALP and FLV using a column-switching, high-performance liquid chromatographic method with ultraviolet detection. The CYP2C19(*)2 or CYP2C19(*)3 alleles were identified using a polymerase chain reaction analysis. RESULTS: Coadministration with FLV produced significant, on average 58%, increases in the plasma concentrations of ALP ( P<0.001). There were, however, wide variations in the interactive effects of the coadministration of FLV on the plasma concentrations of ALP. While there were some subjects who had greater increases in plasma ALP concentrations, more than 100%, in response to the coadministration of FLV among the subjects with no mutated or one mutated allele, there are no subjects who had increases in plasma ALP concentrations of more than 50% among the subjects with two mutated alleles. The differences of these variances among the three genotype groups reached a level of significance ( P<0.05). CONCLUSION: Coadministration of FLV significantly increased the plasma concentrations of ALP compared with ALP monotherapy. Wide variations were observed in the drug interactions, with the CYP2C19 genotype possibly being related to these interactions.

Adult↗
PubMed2002

Decreased levels of brain-derived neurotrophic factor in serum of chronic schizophrenic patients.

Neurotrophic factors regulate neuronal development as well as synaptic plasticity, and their impairment is often implicated as a cause of schizophrenia. Among various neurotrophic molecules, brain-derived neurotrophic factor (BDNF) levels have been found to be increased in the corticolimbic regions of patients' brains. In the present study, we assessed peripheral BDNF levels in whole blood as well as in the serum of two independent groups of schizophrenic patients (n = 34 in each group) and healthy volunteers (n = 35 and n = 27, respectively). BDNF protein levels in fresh serum and blood of the patients and volunteers were measured using a two-site enzyme immunoassay and correlated with the number and decay of platelets. In addition to the studies of patients and volunteers, neuroleptic effects on BDNF levels were assessed by administering haloperidol to adult rats for 2 weeks or 5 months. The major findings were as follows: BDNF levels were significantly reduced in the serum of schizophrenic patients (P < 0.005, Mann-Whitney U-test) but not in their whole blood. Antipsychotic dose did not correlate with serum BDNF levels. Moreover, chronic administration of haloperidol failed to decrease serum BDNF levels in adult rats. Abnormal levels of BDNF are evident not only in the brain of schizophrenic patients, but also in their peripheral blood. The BDNF reduction in serum but not in whole blood suggests a potential deficit in neurotrophic factor release in patients with schizophrenia.

Adult↗
PubMed2002

Isolation and structure of the mouse 14-3-3 eta chain gene and the distribution of 14-3-3 eta mRNA in the mouse brain.

14-3-3 protein is a brain-specific protein discovered by Moore and Perez, but at present is thought to be a multifunctional protein. To clarify the brain-specific function of the protein, we intend constructing a 14-3-3 eta gene knock-out mouse. As the first step of this process, we isolated the mouse 14-3-3 eta chain gene and determined its structure. The mouse gene is about 10 kb long and composed of two exons separated by a long intron. The transcription start site was identified and the polyadenylation signals (AATAAA) were found in exon 2 of the mouse gene. In the 5'-upstream sequence, we found several cis elements including a CRE sequence, a TATA box-like sequence, and a C/EBP element. Furthermore, the distribution of 14-3-3 eta mRNA in the mouse brain was examined by in situ hybridization histochemistry. The highest signals were found in the Purkinje cells of the cerebellum, the pyramidal cells of the hippocampus and the olfactory bulb neurons of the adult mouse. Neuronal expression of 14-3-3 eta in these regions mRNA may generally increase during postnatal brain development. The distribution of protein kinase C gamma in the mouse brain was also examined by immunohistochemistry. From the distribution of 14-3-3 eta mRNA and protein kinase C gamma in the mouse brain, the involvement of these compounds in the induction and maintenance of LTP was discussed.

14-3-3 Proteins↗