Biomedical subjects

H Ujike

Publications and source records attributed to H Ujike.

At least 19 recordsLinked to original sources

PubMed2007

Possible association of beta-arrestin 2 gene with methamphetamine use disorder, but not schizophrenia.

Recent investigations suggest that the AKT/glycogen synthase kinase 3 (GSK3) signaling cascade may be associated with the pathophysiology of schizophrenia and methamphetamine (METH) use disorder. One important molecule related to this cascade is beta-arrestin 2 (ARRB2). We therefore conducted a genetic case-control association analysis of the gene for ARRB2 with schizophrenia and METH use disorder in a Japanese population (547 people with schizophrenia, 177 with METH use disorder and 546 controls). A possible association of 'tag single nucleotide polymorphisms (SNPs)' was found in METH use disorder (rs1045280: P(genotype) = 0.0118, P(allele) = 0.00351; rs2036657: P(allele) = 0.0431; rs4790694: P(genotype) = 0.0167, P(allele) = 0.0202), but no association was found with schizophrenia. We also evaluated the gene-gene interactions among ARRB2, AKT1, and GSK3B, which we previously reported for each of these diseases. However, no interaction was seen in our samples. This is the first association analysis of ARRB2, and our results indicate that ARRB2 may play a role in the pathophysiology of METH use disorder.

Adult↗

PubMed2006

RGS4 is not a susceptibility gene for schizophrenia in Japanese: association study in a large case-control population.

The regulator of the G-protein signaling 4 (RGS4) has been implicated in the susceptibility to schizophrenia. RGS4 interacts with ErbB3 that acts as receptors for neuregulin 1 and these proteins may play a role in the pathogenesis of schizophrenia via glutamatergic dysfunction. Recently, two meta-analysis studies provided different interpretations for the genetic association between RGS4 and schizophrenia. We attempted to confirm this association in a case-control study of 1918 Japanese patients with schizophrenia and 1909 Japanese control subjects. Four widely studied single nucleotide polymorphisms (SNPs) were genotyped, and none showed association with schizophrenia. SNP 1 (rs10917670), p=0.92; SNP 4 (rs951436), p=0.91; SNP 7 (rs951439), p=0.27; and SNP 18 (rs2661319), p=0.43. A haplotype block constructed by these SNPs spans the 5' flanking region to the 5' mid-region of the RGS4 gene. Previous meta-analysis showed that both two major haplotypes of this block were risk haplotypes. The two common haplotypes were observed in the Japanese population. However, neither haplotype was significantly associated with schizophrenia. We conclude that the common haplotypes and SNPs of the RGS4 gene identified thus far are unlikely to contribute to the genetic susceptibility to schizophrenia in the Japanese population.

Adult↗

PubMed2006

Identification and haplotype analysis of LRRK2 G2019S in Japanese patients with Parkinson disease.

LRRK2 G2019S is the most common known cause of Parkinson disease (PD) in patients of European origin, but little is known about its distribution in other populations. The authors identified two of 586 Japanese patients with PD heterozygous for the mutation who shared a haplotype distinct from that observed in Europeans. This suggests that G2019S originated from separate founders in Europe and Japan and is more widely dispersed than previously recognized.

Adolescent↗

PubMed2006

Serine racemase binds to PICK1: potential relevance to schizophrenia.

Accumulating evidence from both genetic and clinico-pharmacological studies suggests that D-serine, an endogenous coagonist to the NMDA subtype glutamate receptor, may be implicated in schizophrenia (SZ). Although an association of genes for D-serine degradation, such as D-amino acid oxidase and G72, has been reported, a role for D-serine in SZ has been unclear. In this study, we identify and characterize protein interacting with C-kinase (PICK1) as a protein interactor of the D-serine synthesizing enzyme, serine racemase (SR). The binding of endogenous PICK1 and SR requires the PDZ domain of PICK1. The gene coding for PICK1 is located at chromosome 22q13, a region frequently linked to SZ. In a case-control association study using well-characterized Japanese subjects, we observe an association of the PICK1 gene with SZ, which is more prominent in disorganized SZ. Our findings implicating PICK1 as a susceptibility gene for SZ are consistent with a role for D-serine in the disease.

Adult↗

PubMed2006

Association study of the dihydropyrimidinase-related protein 2 gene and methamphetamine psychosis.

Dihydropyrimidinase-related protein 2 (DRP-2 or DPYSL-2)mediates the intracellular response to collapsin, a repulsive extracellular guidance cue or axonal outgrowth. DRP-2 is also referred to as collapsin response mediator protein 2 (CRMP-2). We have previously demonstrated that the DRP-2 gene is associated with susceptibility to schizophrenia, but not to bipolar disorders. In addition, a genetic association was observed with paranoid-type schizophrenia, but not with hebephrenic-type schizophrenia. It has been well documented that repeated abuse of methamphetamine (METH) for a long period frequently produces psychotic symptoms, such as auditory hallucinations and delusions that are hardly distinguishable from those of paranoid-type schizophrenia. Therefore, we hypothesized that a certain genetic variant of the DRP-2 gene may affect individual vulnerability to the development of METH-induced psychosis. We examined the genetic association by a case-control method. The polymorphism *2236T>C in the 3' untranslated region of the DRP-2 gene, which has been shown to be a negative genetic risk factor for paranoid-type schizophrenia, was analyzed in 198 patients with METH psychosis and 221 corresponding healthy controls in a Japanese population. No significant association of the DRP-2 gene with METH psychosis was found. Neither did we find an association with the clinical phenotype of METH psychosis, such as the age of first consumption of METH, latency to development of psychosis after METH abuse, prognosis of psychosis after detoxification from METH use, complication of spontaneous relapse of psychosis without reconsumption of the drug, or multisubstance abuse status. These findings indicate that a genetic variant of the DRP-2 gene may not affect the risk of METH psychosis or any clinical phenotype of the disorder.

Adult↗

PubMed2006

Association study of the tumor necrosis factor-alpha gene and its 1A receptor gene with methamphetamine dependence.

Recent preclinical findings that repeated treatment with methamphetamine (METH) induced an increase in tumor necrosis factor-alpha (TNF-alpha) mRNA in some brain regions and that TNF-alpha blocked METH neurotoxicity and rewarding effects suggest TNF-alpha, a multifunctional pro-inflammatory cytokine, may be involved in METH dependence. We hypothesized that genetic polymorphisms of the TNF-alpha gene and its receptor genes may be associated with vulnerability to METH dependence. Genetic association of -308G>A and -857C>T in the promotor region of the TNF-alpha gene, and 36A>G in exon 1 of the TNF receptor 1A gene (TNFR-SF1A), were analyzed in patients with METH dependence (n = 185) and healthy controls (n = 221) in a Japanese population. No significant association of alleles or haplotypes of the TNF-alpha or TNFR-SF1A genes with METH dependence was found. Neither was any significant association of clinical phenotype with METH dependence found. These results suggest that genetic variations in the TNF-alpha gene and its receptor genes may not be involved in individual vulnerability to METH dependence.

Adult↗

PubMed2006

No association between CART (cocaine- and amphetamine-regulated transcript) gene and methamphetamine dependence.

Cocaine- and amphetamine-regulated transcript (CART) was originally discovered as a peptide that increased in the rat striatum after injection of a psychostimulant drug, such as cocaine or amphetamine, and is suggested to play potential roles in drug dependence. We tested the genetic association between the CART gene and methamphetamine (METH) dependence and/or psychosis. The subjects were 203 patients with METH dependence and 239 age- and gender-matched healthy controls. Two single nucleotide polymorphisms (SNPs) of the CART gene, -156A>G and IVS1 + 224G>A, were examined . There were no significant differences in genotype and allele distributions of the polymorphisms between patients with METH dependence and/or psychosis and controls. Neither were significant differences in subgroups of clinical phenotypes, for example, age at first consumption of METH, latency to onset of psychotic symptoms after the first consumption of METH, prognosis of psychosis after therapy, complication of spontaneous relapse to a psychotic state, or multisubstance abuse status, observed. The present findings suggest that the CART gene may not play a pivotal role in the development of METH dependence and psychosis, at least in a Japanese population.

Adult↗

PubMed2005

Haplotype association between GABAA receptor gamma2 subunit gene (GABRG2) and methamphetamine use disorder.

Psychostimulant use disorder and schizophrenia have a substantial genetic basis. Evidence from human and animal studies on the involvement of the gamma-aminobutyric acid (GABA) system in methamphetamine (METH) use disorder and schizophrenia is mounting. As we tested for the association of the human GABA(A) receptor gamma 2 subunit gene (GABRG2) with each diagnostic group, we used a case-control design with a set of 178 subjects with METH use disorder, 288 schizophrenics and 288 controls. First, we screened 96 controls and identified six SNPs in GABRG2, three of whom we newly reported. Next, we selected two SNPs, 315C>T and 1128+99C>A, as representatives of the linkage disequilibrium blocks for further case-control association analysis. Although no associations were found in either allelic or genotypic frequencies, we detected a haplotypic association in GABRG2 with METH use disorder, but not with schizophrenia. This finding partly replicates a recent case-control study of GABRG2 in METH use disorder, and thus indicates that GABRG2 may be one of the susceptibility genes of METH use disorder.

Adolescent↗

PubMed2004

No association is found between the candidate genes of t-PA/plasminogen system and Japanese methamphetamine-related disorder: a collaborative study by the Japanese Genetics Initiative for Drug Abuse.

In the central nervous system, tissue-plasminogen activator (t-PA)/plasmin system is involved in long-term synaptic plasticity and remodeling, and participates in rewarding effects of methamphetamine (MAP), by acutely regulating MAP-induced dopamine release in the nucleus accumbens. The aim of this study was to examine the relationships between the patients with MAP abusers/psychosis and the t-PA/plasminogen system genes. Subjects comprised 185 MAP abusers and 288 healthy controls. Four polymorphisms in the t-PA, plasminogen activator inhibitor, and plasminogen genes were examined in the present study. No significant differences were observed in each polymorphism between healthy controls and MAP abusers/psychosis. This study suggests that t-PA/plasminogen system is unlikely to be a major contributor to the substance abuse liability and/or the development of MAP psychosis.

Amphetamine-Related Disorders↗

PubMed2004

A polymorphism of DRD2 gene and brain atrophy in methamphetamine psychosis.

Our group, Ujike et al., recently reported that the A1 allele of TaqI A polymorphism of the dopamine receptor D2 (DRD2) gene, associated with transient psychosis, significantly differs from that of patients with prolonged psychosis in methamphetamine psychosis. Therefore, we examined the association between the TaqI A polymorphism of the DRD2 gene and the brain MRI view for patients with methamphetamine psychosis. The subjects underwent brain MRI scans using the FLAIR method. Genotyping was performed by PCR-RFLP methods using genomic DNA extracted from peripheral blood by the phenol method. Ten subjects had the A1/A2 genotype, eleven subjects had the A2/A2 genotype, and no subject had the A1/A1 genotype. The domain size, including the thalamus and basal ganglia that were inside each side of the putamens, did not differ between the three groups (the A1/A2-group, the A2/A2-group, and the young healthy person group). In the comparison based on this domain, the temporal lobe tended to narrow in the A2/A2-group compared to the A1/A2-group (P = .06). The other domain (cerebrum, corpus callosum, etc.) showed no difference between the A1/A2-group and the A2/A2-group. It is suggested that in methamphetamine psychosis the TaqI A polymorphism not only regulates prolongation of psychosis symptoms but also influences the form of the temporal lobe.

Adult↗

PubMed2003

Nine- or fewer repeat alleles in VNTR polymorphism of the dopamine transporter gene is a strong risk factor for prolonged methamphetamine psychosis.

Susceptibility to drug dependence and drug-induced psychoses is influenced not only by the pharmacological effects of the drug but also by the genetic factors of the individual. To clarify the latter, we investigated the association between methamphetamine (METH) dependence/psychosis and the hDAT1 gene (SLC6A3) encoding the dopamine transporter, which is the primary site of METH activity in the brain. Four exonic polymorphisms of the hDAT1 gene, 242C/T (exon 2), 1342A/G (exon 9), 2319G/A (3'UTR), and VNTR (3'UTR) were examined. Although there was no significant difference in genotypic and allelic distribution of the four polymorphisms between all METH dependence/psychosis patients (N=124) and controls (N=160), the patients with METH psychosis lasting for 1 month or more after discontinuance of METH consumption showed a significant excess of nine- or fewer repeat alleles of the VNTR in 3'UTR of the hDAT1 gene (P=0.0054, OR=4.24, 95% CI=2.46-7.31). The present study demonstrated that the presence of nine- or fewer repeat alleles of hDAT1 is a strong risk factor for a worse prognosis of METH psychosis.

Adult↗

PubMed2002

CNR1, central cannabinoid receptor gene, associated with susceptibility to hebephrenic schizophrenia.

To examine the cannabinoid hypothesis for pathogenesis of schizophrenia, we examined two kinds of polymorphisms of the CNR1 gene, which encodes human CB1 receptor, a subclass of central cannabinoid receptors, in schizophrenics and age-matched controls in the Japanese population. Allelic and genotypic distributions of polymorphism 1359G/A at codon 453 in the coding region and AAT triplet repeats in the 3' flanking region in the Japanese population were quite different from those in Caucasians. Although the polymorphism 1359G/A was not associated with schizophrenia, the triplet repeat polymorphism of the CNR1 gene was significantly associated with schizophrenia, especially the hebephrenic subtype (P = 0.0028). Hebephrenic schizophrenia showed significantly increased rate of the 9 repeat allele (P = 0.032, OR = 2.30, 95% CI (1.91-2.69)), and decreased rate of the 17 repeat allele (P = 0.011, OR = 0.208, 95% CI (0.098-0.439)). The present findings indicated that certain alleles or genotypes of the CNR1 gene may confer a susceptibility of schizophrenia, especially of the hebephrenic type.

Adult↗

PubMed2001

Effects of subchronic lithium chloride treatment on G-protein subunits (Golf, Ggamma7) and adenylyl cyclase expressed specifically in the rat striatum.

Lithium salt has been widely used as a treatment for mania, but the mechanism of its effect remains unknown. Previously, by studying c-fos expression, we showed that the striatum was a possible target region for the antimanic effects of lithium salt. The present study focused on the effect of subchronic lithium chloride treatment on G-proteins (Golf, Ggamma7) and adenylyl cyclase type V, which are expressed specifically in the rat striatum. Subchronic lithium chloride treatment significantly increased the level of Golf protein, a stimulant alpha-subunit of G-protein, by 53.5% (P<0.01), but the levels of Ggamma7 and adenylyl cyclase type V did not change. This increased level of Golf protein was found after 2 weeks of lithium chloride treatment, but not after 1 week, and the level returned to the basal level 1 week after withdrawal of lithium chloride. This result suggests that the level of Golf protein increases to compensate for the suppression of the adenylyl cyclase system by lithium, and that this increase may account for the "rebound" phenomenon, which is the relapse observed after abrupt discontinuation of lithium salt treatment.

Adenylyl Cyclases↗

PubMed2001

Increased expression of synaptophysin and stathmin mRNAs after methamphetamine administration in rat brain.

The rearrangement of neural networks associated with the behavioral sensitization induced by psychostimulants is poorly understood. We have investigated the effect of methamphetamine (METH) administration on the mRNA levels of three different classes of plasticity-related genes in the rat brain. The expression of synaptophysin mRNA increased 20-40% in the nucleus accumbens, prefrontal and temporal cortices, 1-24 h after acute METH administration, and that of stathmin mRNA increased about 20% in the prefrontal cortex 1 h later. They did not change after subchronic administration. The level of alpha-tubulin mRNA was constant. Therefore, synaptophysin and stathmin play an important role in the neural plastic changes involved in the early induction process of METH-induced sensitization, but not in the later maintenance process.

Animals↗

PubMed2001

Association study of CAG repeats in the KCNN3 gene in Japanese patients with schizophrenia, schizoaffective disorder and bipolar disorder.

To investigate a possible involvement of expanded triplet repeats of genome in the genomes of patients with endogenous psychoses, we examined a CAG repeat polymorphism in the coding region of the KCNN3 gene in schizophrenia, schizoaffective disorder, bipolar disorder and controls of the Japanese population. There were no significant differences in the CAG repeat number of longer or shorter alleles among the four diagnostic groups or among the schizophrenia hebephrenic and paranoid subtypes.

Adenine↗

PubMed2001

NOTCH4 gene polymorphism and susceptibility to schizophrenia and schizoaffective disorder.

The NOTCH4 gene is located at 6p21.3, a site which several studies have shown to have significant linkage with schizophrenia. Recently, an exceptionally strong association was reported between NOTCH4 gene polymorphisms and schizophrenia in British patients. We re-examined their findings using a Japanese population. We genotyped three kinds of polymorphisms, SNP1 in the 5' flanking region, SNP2 in the promoter region and CTG repeats in exon 1 of the NOTCH4 gene of schizophrenics (N=188), patients with schizoaffective disorder (N=39) and controls (N=143). Genotypic distributions and allelic frequencies of SNP1, SNP2 and CTG repeats of the NOTCH4 gene did not show significant associations with schizophrenia or schizoaffective disorder. Neither they showed association with schizophrenia subcategories, hebephrenic and paranoid type schizophrenia, nor with subgroups of schizophrenia with and without positive family history of psychoses. The present study found that the NOTCH4 gene does not confer susceptibility to schizophrenia and schizoaffective disorders, at least in Japanese subjects, in contrast to the findings in British subjects.

Adult↗

PubMed2001

Familial amyotrophic lateral sclerosis with a novel Leu126Ser mutation in the copper/zinc superoxide dismutase gene showing mild clinical features and lewy body-like hyaline inclusions.

BACKGROUND: Mutations in the SOD1 gene are responsible for approximately 25% of all familial amyotrophic lateral sclerosis (ALS) cases. However, the correlation between the clinical and pathological features and the various SOD1 gene mutations has not been well characterized. OBJECTIVES: To screen the SOD1 gene in search of potential mutations and to obtain clinical and pathological data for 2 Japanese families with ALS. DESIGN: Clinical histories and neurological findings, gross and microscopic pathological features, and DNA analysis of the SOD1 gene. RESULTS: The 2 families with ALS showed a novel missense mutation in the SOD1 gene, which was heterozygous for point mutation TTG to TCG, causing substitution of leucine for serine at codon 126 (Leu126Ser) in exon 5. Clinically, patients showed slower disease progression and lack of upper motor neuron signs. Neuropathologically, the autopsied patient showed the form of familial ALS with posterior column involvement, and the pontocerebellar tract and the dentate nuclei of the cerebellum were also involved. Furthermore, abundant Lewy body-like hyaline inclusions were observed in the affected motor and nonmotor neurons. CONCLUSIONS: Familial ALS with a novel Leu126Ser mutation in the SOD1 gene showed mild clinical features and lack of upper motor neuron signs. We believe that Leu126Ser might be associated with the clinical features and that the mutation site in the SOD1 gene and disease duration might be associated with the formation of Lewy body-like hyaline inclusions.

Adult↗

PubMed2001

A family with X-linked dystonia-deafness syndrome with a novel mutation of the DDP gene.

BACKGROUND: X-linked dystonia-deafness syndrome (DDS) is characterized by early-onset deafness followed by progressive dystonia in adulthood. Only 4 families with the syndrome have been reported, and all were white. OBJECTIVE: To describe the first nonwhite family with X-linked DDS, involving 5 affected males in 4 generations. RESULTS: Clinical features of the family members, who were Japanese, were mostly consistent with reports of DDS in whites except for a lack of visual disturbances. Whereas microdeletions in the deafness-dystonia peptide (DDP) gene were found in 2 white DDS families, our patients showed a novel mutation (arg80ter) in exon 2 of the DDP gene. CONCLUSION: The existence of a DDS family of Japanese origin with a new kind of mutation in the DDP gene provides additional evidence that the DDP gene is a causative gene for X-linked DDS.

Adolescent↗