Biomedical subjects

Kenji Nakata

Publications and source records attributed to Kenji Nakata.

11 recordsLinked to original sources

PubMed2005

Induction of OGG1 gene expression by HIV-1 Tat.

To identify the cellular gene target for Tat, we performed gene expression profile analysis and found that Tat up-regulates the expression of the OGG1 (8-oxoguanine-DNA glycosylase-1) gene, which encodes an enzyme responsible for repairing the oxidatively damaged guanosine, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG). We observed that Tat induced OGG1 gene expression by enhancing its promoter activity without changing its mRNA stability. We found that the upstream AP-4 site within the OGG1 promoter is responsible and that Tat interacted with AP-4 and removed AP-4 from the OGG1 promoter by in vivo chromatin immunoprecipitation assay. Thus, Tat appears to activate OGG1 expression by sequestrating AP-4. Interestingly, although Tat induces oxidative stress known to generate 8-oxo-dG, which causes the G:C to T:A transversion, we observed that the amount of 8-oxo-dG was reduced by Tat. When OGG1 was knocked down by small interfering RNA, Tat increased the amount of 8-oxo-dG, thus confirming the role of OGG1 in preventing the formation of 8-oxo-dG. These findings collectively indicate the possibility that Tat may play a role in maintenance of the genetic integrity of the proviral and host cellular genomes by up-regulating OGG1 as a feed-forward mechanism.

Binding Sites↗

PubMed2005

Association study between brain-derived neurotrophic factor gene polymorphisms and methamphetamine abusers in Japan.

Several lines of evidence suggest that genetic factors might contribute to drug abuse vulnerability. Recent genomic scans for association demonstrated that the brain-derived neurotrophic factor (BDNF) gene was associated with drug abuse vulnerability. In this study, we analyzed association of two BDNF gene single nucleotide polymorphisms (SNPs), 132C > T (C270T named formerly) in the noncoding region of exon V and 196G > A (val66met) in the coding region of exon XIIIA, with methamphetamine (MAP) abuse in Japan. No significant differences were found in the frequency of the genotype or allele in these two SNPs between MAP abusers and controls (132C > T in exon V: genotype, P = 0.586, allele, P = 0.594; 196G > A (val66met) in exon XIIIA: genotype, P = 0.889, allele, P = 0.713). Furthermore, there was no difference between clinical parameters (e.g., prognosis psychosis, spontaneous relapse, or poly-substance abuse) and the two SNPs of BDNF gene. These results suggest that the two SNPs (132C > T in exon V and 196G > A (val66met) in exon XIIIA) of the BDNF gene may not be associated with Japanese MAP abusers. This article contains supplementary material, which may be viewed at the American Journal of Medical Genetics website at http://www.interscience.wiley.com/jpages/0148-7299:1/suppmat/index.html.

Adult↗

PubMed2004

No association between the insulin degrading enzyme gene and Alzheimer's disease in a Japanese population.

Susceptibility to Alzheimer's disease (AD) is thought to be regulated by multiple genetic factors. Recently, three independent studies have reported that loci on chromosome 10q are linked with AD, and the insulin degrading enzyme (IDE; MIM 146680) gene located on chromosome 10q23-q25; IDE is located close to the maker D10S583, which exhibits a maximum LOD score for late-onset AD. We examined seven polymorphisms in the IDE gene, the marker D10S583 in the 5' flanking region, and SNPs in introns 1, 3, 11, 20, 21, and 22 (rs#1999764, 1855915, 1970244, 538469, 551266, and 489517, respectively). Four SNPs in introns 3, 11, 20, and 22 did not exhibit any polymorphisms in the Japanese population that was studied. D10S583 and two SNPs in introns 1 and 21 did not exhibit a significant association with early- or late-onset AD. In addition, no associations were observed for subgroups of AD grouped according to APOE status. The present study indicates that the IDE gene polymorphisms do not confer susceptibility to early- or late-onset AD at least in a Japanese population.

Aged↗

PubMed2004

Association of the Neprilysin gene with susceptibility to late-onset Alzheimer's disease.

Neprilysin (NEP), also known as neutral endopeptidase, enkephalinase, CD 10, and common acute lymphoblastic leukemia antigen, is a 97-kD protein. NEP can degrade amyloid beta peptides, and its mRNA and protein levels are known to be reduced in the brains of patients with Alzheimer's disease (AD), making the NEP gene a substantial candidate for an AD risk factor. We examined the genetic association of three NEP polymorphisms, a GT-repeat polymorphism and two single nucleotide polymorphisms (SNPs, -1075A>G and -1284G>C) in its promoter region, with AD in a Japanese case-control sample (240 patients and 163 controls). The GT-repeat polymorphism, but not the SNPs, was significantly associated with late-onset AD (p = 0.0007). Our findings suggest that the GT-repeat polymorphism in the promoter region of the NEP gene or some other unknown polymorphisms, which are in a linkage disequilibrium, confer a susceptibility to late-onset AD.

Age of Onset↗

PubMed2004

[The human dihydropyrimidinase-related protein 2 (DRP-2) gene on chromosome 8p21 is associated with paranoid-type schizophrenia].

The dihydropyrimidinase-related protein (DRP) family, also called the collapsin response mediator protein, is implicated in the developmental process of the nervous system. Dysfunction of DRPs may result in neurodevelopmental abnormalities, which have been assumed to be a possible factor in the pathogenesis of schizophrenia. It has been reported that in humans, the expression of one member of the DRP family, DRP-2, is decreased in the brains of individuals with schizophrenia. In addition, the DRP-2 gene is located on chromosome 8p21, a region that has been implicated in schizophrenia in genetic linkage studies. We investigated a genetic association between five polymorphisms of the DRP-2 gene and schizophrenia in the Japanese population. The *2236T > C polymorphism in the 3' untranslated region (3'UTR) exhibited significant differences with respect to the distribution of the genotype and allele in patients compared with controls. The frequency of the *2236C allele was significantly higher in controls than in patients with schizophrenia (P = 0.0097) and patients with paranoid-type schizophrenia (P = 0.0083). These results suggest that the *2236C allele in the 3'UTR of the DRP-2 gene, or an unknown mutation in linkage disequilibrium with this allele, may reduce the susceptibility to schizophrenia, especially the paranoid subtype.

Alleles↗

PubMed2003

The human frizzled-3 (FZD3) gene on chromosome 8p21, a receptor gene for Wnt ligands, is associated with the susceptibility to schizophrenia.

Neurodevelopmental abnormalities have been reported in studies on the pathogenesis of schizophrenia. The Wnt-signaling pathway has been implicated in a variety of processes in neurodevelopment, and the frizzled proteins have been identified as receptors for Wnt ligands. Of the frizzled proteins, frizzled-3 (FZD3) is required for formation of the neural crest and for development of major fiber tracts in the CNS. The human FZD3 gene is located on chromosome 8p21, a positive linkage locus for schizophrenia. We analyzed polymorphisms of the FZD3 gene in patients with schizophrenia and control subjects in the Japanese population. We found a significant association between schizophrenia and the FZD3 gene in single nucleotide polymorphisms and haplotype analyses. Our data suggest that dysregulation of the Wnt-signaling pathway may be involved in the susceptibility to schizophrenia.

Adult↗

PubMed2003

No association between the sigma receptor type 1 gene and schizophrenia: results of analysis and meta-analysis of case-control studies.

BACKGROUND: Several lines of evidence have supported possible roles of the sigma receptors in the etiology of schizophrenia and mechanisms of antipsychotic efficacy. An association study provided genetic evidence that the sigma receptor type 1 gene (SIGMAR1) was a possible susceptibility factor for schizophrenia, however, it was not replicated by a subsequent study. It is necessary to evaluate further the possibility that the SIGMAR1 gene is associated with susceptibility to schizophrenia. METHODS: A case-control association study between two polymorphisms of the SIGMAR1 gene, G-241T/C-240T and Gln2Pro, and schizophrenia in Japanese population, and meta-analysis including present and previous studies. RESULTS: There was no significant association of any allele or genotype of the polymorphisms with schizophrenia. Neither significant association was observed with hebephrenic or paranoid subtype of schizophrenia. Furthermore, a meta-analysis including the present and previous studies comprising 779 controls and 636 schizophrenics also revealed no significant association between the SIGMAR1 gene and schizophrenia. CONCLUSION: In view of this evidence, it is likely that the SIGMAR1 gene does not confer susceptibility to schizophrenia.

Asian People↗

PubMed2003

No association between the dihydropyrimidinase-related protein 2 (DRP-2) gene and bipolar disorder in humans.

Several susceptibility loci for both of schizophrenia and bipolar disorder (BPD) have been found to overlap on several chromosomes including 8p21. Expression of dihydropyrimidinase-related protein 2 (DRP-2), which gene is located on 8p21, was found to be reduced in the brains of individuals with schizophrenia and BPD. Recently, we demonstrated a significant association between the DRP-2 gene and schizophrenia. Based on the rationale, we investigated the genetic association of the DRP-2 gene with BPD using a case-control study in the Japanese population. However, no significant associations were found between five polymorphisms of the DRP-2 gene (-975C>G, 352G>A, 426C>T, 1506T>C, and *2236T>C), and BPD, nor were associations detected between either of the polymorphisms and any subtype of BPD, bipolars I and II. The present study did not provide any evidence for a contribution of the DRP-2 gene to susceptibility to BPD.

Adult↗

PubMed2003

The human dihydropyrimidinase-related protein 2 gene on chromosome 8p21 is associated with paranoid-type schizophrenia.

BACKGROUND: The dihydropyrimidinase-related protein (DRP) family, also called the collapsin response mediator protein, is implicated in the developmental process of the nervous system. Dysfunction of DRPs may result in neurodevelopmental abnormalities, which may be a factor in the pathogenesis of schizophrenia. The expression of one member of DRP-2 in humans has been reported to be decreased in the brains of people with schizophrenia. In addition, the DRP-2 gene (Dihydropyrimidinase-like 2; DPYSL2) is located on chromosome 8p21, a region that has been implicated in schizophrenia in genetic linkage studies. METHODS: We investigated a genetic association between five polymorphisms of the DRP-2 gene and schizophrenia in the Japanese population. RESULTS: The *2236T>C polymorphism in the 3' untranslated region (3'UTR) exhibited significant differences with respect to the distribution of the genotype and allele in patients compared with control subjects. The frequency of the *2236C allele was significantly higher in control subjects than patients with schizophrenia (p =.0097) and paranoid-type schizophrenia (p =.0083). CONCLUSIONS: Our results suggest that the *2236C allele in the 3'UTR of the DRP-2 gene, or an unknown mutation in linkage disequilibrium with this allele, may reduce the susceptibility to schizophrenia, especially the paranoid subtype.

Alleles↗

PubMed2003

Association study of the brain-derived neurotrophic factor (BDNF) gene with bipolar disorder.

Brain-derived neurotrophic factor (BDNF) belongs to a family of neurotrophic factors and has been demonstrated to promote the survival, differentiation, and maintenance of a broad variety of central nervous system neurons. Several reports have suggested that the BDNF gene is a plausible functional candidate gene underlying the predisposition for developing bipolar disorder (BPD). In the present study, we investigated the possible role of the BDNF gene in the etiology of BPD using a matched case-control association design in a Japanese population. There was no evidence for an allelic or genotypic association of two polymorphisms (-1360C>T and 196G>A) of the BDNF gene with BPD. Furthermore, no significant association was observed between these polymorphisms and either of two diagnostic subtypes (bipolars I and II disorder). The results suggest that the BDNF gene is unlikely to confer susceptibility to BPD.

Bipolar Disorder↗

PubMed2003

Association study between the fibronectin gene and schizophrenia.

Fibronectin is one of the cell adhesion proteins. Adhesion molecules play an important role in neural and synaptic genesis, and their dysfunction may result in neurodevelopmental abnormalities, which have been assumed to be a factor in the pathogenesis of schizophrenia. To examine the possible involvement of fibronectin in the etiology of schizophrenia, we analyzed six polymorphisms, located in introns 2, 21, 24, and 26, and exons 20 and 28, in the human fibronectin gene (FN1) of schizophrenic patients in the Japanese population (n = 104) and age-and gender-matched controls (n = 104). No significant positive association was observed between either of the polymorphisms and schizophrenia, nor was an association found between either of the polymorphisms and any subtypes of schizophrenia. These data did not provide evidence for a contribution of the FN1 gene to susceptibility to schizophrenia.

Adult↗