Biomedical subjects

Norio Ozaki

Publications and source records attributed to Norio Ozaki.

At least 19 recordsLinked to original sources

PubMed2007

Association study of polymorphisms in the glutamate transporter genes SLC1A1, SLC1A3, and SLC1A6 with schizophrenia.

Based on the glutamatergic dysfunction hypothesis for schizophrenia pathogenesis, we have been performing systematic association studies of schizophrenia with the glutamate receptor and transporter genes. We report here association studies of schizophrenia with three glutamate transporter genes SLC1A1, SLC1A3, and SLC1A6 encoding the glutamate transporters EAAT3, EAAT1, and EAAT4, respectively. We initially performed the screening of the total 25 single nucleotide polymorphisms (SNPs) distributed in the three gene regions using 100 out of 400 Japanese cases and 100 out of 420 Japanese controls. After controlling the false discovery rate (FDR) at level 0.05, we observed significant associations of schizophrenia with a genotype of SNP4 (rs2097837, P = 0.007) and with haplotypes of SNP2-SNP5 (P = 7.5 x 10(-5)) and SNP3-SNP5 (P = 9.0 x 10(-4)) in the SLC1A6 region. The haplotype of SNP2-SNP5 of SLC1A6 even showed marginally significant association with the disease in the full-size sample (400 cases and 420 controls, P = 0.031). We concluded that at least one susceptibility locus for schizophrenia may be located within or nearby SLC1A6, whereas SLC1A1 and SLC1A3 are unlikely to be major susceptibility genes for schizophrenia in the Japanese population.

Adult↗

PubMed2006

Gene-gene interaction analysis of personality traits in a Japanese population using an electrochemical DNA array chip analysis.

It has been suggested that genes involved in the central dopaminergic pathway may contribute to personality traits. However, the results of association studies for these genes have not been consistent. The present study investigated the relationship between the specific polymorphisms of MAO-A, COMT, DRD2, DRD3 and personality traits in Japanese women using a novel genotyping method involving electrochemical DNA array (ECA) chip analysis. Single marker association analysis for each mutation revealed no significant association between scores for Neuroticism Extraversion Openness-Five Factor Inventory (NEO-FFI) items. Gene-gene interaction analysis showed that a MAO-A 30-bp repeatxCOMT (Val158Met)xDRD3 (Ser9Gly) had a marginally significant association with Agreeableness (P=0.0547). The present results suggest that a combination of polymorphisms of MAO-A, COMT, and DRD3 might affect personality traits in Japanese women.

Adolescent↗

PubMed2006

Factors contributing to sleep disturbance and hypnotic drug use in hemodialysis patients.

OBJECTIVE: Sleep disturbance and the use of hypnotic medications are common in patients on hemodialysis. Factors that contribute to sleep disturbance and the use of hypnotic medications in hemodialysis patients were investigated. METHODS: With the use of a questionnaire-based survey, we examined the prevalence of symptoms that reflect sleep disorders such as insomnia, restless legs syndrome (RLS), and snoring and use of hypnotic medications in 252 hemodialysis patients. RESULTS: The overall prevalence of insomnia was 59.1%, with the prevalence of difficulty in initiating sleep (DIS), difficulty in maintaining sleep (DMS), and early morning awakening (EMA) being 47.6, 24.2, and 28.2%, respectively. Daytime sleepiness and habitual snoring were reported by 42.5 and 33.7%, respectively. The prevalence of routine use of hypnotic drugs was 25.8%. Both RLS and age were significantly associated with insomnia [odds ratio (OR), 3.75; p 0.001, OR, 1.03; p < 0.01]. RLS was a significant factor for DIS, DMS, and EMA (OR, 2.26; p < 0.05, OR, 3.44; p < 0.0005, OR, 4.25; p < 0.0005) and age was a significant factor for DMS and EMA (OR, 1.03; p = 0.053, OR, 1.05; p < 0.005). Both insomnia and snoring were associated with the use of hypnotic drugs (OR, 2.97; p < 0.001, 1.59; p=0.13). CONCLUSION: Both RLS and sleep-disordered breathing may contribute to sleep disturbance in hemodialysis patients. RLS in particular may be an important factor in insomnia, which in turn is likely responsible for the high prevalence of hypnotic drug use in hemodialysis patients.

Adult↗

PubMed2006

Possible role of preproghrelin gene polymorphisms in susceptibility to bulimia nervosa.

Previous investigations have suggested that ghrelin, an endogenous orexigenic peptide, is involved in the pathology of eating disorders. We conducted a study to determine whether any preproghrelin gene polymorphisms are associated with eating disorders. Three hundred thirty-six eating disorder patients, including 131 anorexia nervosa (AN)-restricting types (AN-R), 97 AN-binge eating/purging types (AN-BP) and 108 bulimia nervosa (BN)-purging types (BN-P), and 300 healthy control subjects participated in the study. Genotyping was performed to determine the polymorphisms present, and with this information, linkage disequilibrium (LD) between the markers was analyzed and the distributions of the genotypes, the allele frequencies, and the haplotype frequencies were compared between the groups. The Leu72Met (408 C > A) (rs696217) polymorphism in exon 2 and the 3056 T > C (rs2075356) polymorphism in intron 2 were in LD (D' = 0.902, r2 = 0.454). Both polymorphisms were significantly associated with BN-P (allele-wise: P = 0.0410, odds ratio (OR) = 1.48; P = 0.0035, OR = 1.63, for Leu72Met and 3056 T > C, respectively). In addition, we observed a significant increase in the frequency of the haplotype Met72-3056C in BN-P patients (P = 0.0059, OR = 1.71). Our findings suggest that the Leu72Met (408 C > A) and the 3056 T > C polymorphisms of the preproghrelin gene are associated with susceptibility to BN-P.

Adult↗

PubMed2006

Volume of left amygdala subregion predicted temperamental trait of harm avoidance in female young subjects. A voxel-based morphometry study.

We investigated the relationship between temperamental predisposition and brain structure by using a standard questionnaire and high-resolution T1-weighted magnetic resonance image (MRI) in normal young volunteers. Fifty-six subjects completed the Japanese version of the Temperament and Character Inventory (TCI, 125 items) and underwent an MRI acquisition of the brain. The gray matter (GM) was extracted from the whole brain image of the subjects and normalized to the standard brain template using statistical parametric mapping and the optimized voxel-based morphometry (VBM) method. When the score on the harm avoidance (HA) subscale was used as a dependent variable, the multiple regression analysis revealed that the HA score positively correlated with the volume of the part of left amygdala. The region-of-interest analysis showed that the correlation was significant in the female subjects but not in the male subjects. The correlation was significant even after the effects of age, depression score, and total GM volume were taken into account. The differential correlation between the sexes may be caused by differences in hormonal condition and the vulnerability of women to socio-psychological stress. In addition, the novelty seeking (NS) score positively correlated with the GM of the left middle frontal gyrus. The volume of the tail of the right caudate nucleus positively correlated with the reward dependence (RD) score. With regard to the NS and RD scores, no significant sex difference was observed in the correlation. These results indicate that the temperamental traits measured using the questionnaire may have a morphological basis in the human brain.

Adult↗

PubMed2006

The G196A polymorphism of the brain-derived neurotrophic factor gene and the antidepressant effect of milnacipran and fluvoxamine.

Prediction of the response to different classes of antidepressants has been an important matter of concern in the field of psychopharmacology. The purpose of the present study was to investigate whether the G196A polymorphism of the brain-derived neurotrophic factor (BDNF) gene is associated with the antidepressant effect of milnacipran, a serotonin norepinephrine reuptake inhibitor, and fluvoxamine, a selective serotonin reuptake inhibitor. The subjects of our previous study of milnacipran (n = 80) and fluvoxamine (n = 54) were included in the present study. Severity of depression was assessed with the Montgomery Asberg depression rating scale (MADRS). Assessments were carried out at baseline and at 1, 2, 4 and 6 weeks of treatment. Polymerase chain reaction was used to determine allelic variants. In all subjects receiving milnacipran or fluvoxamine, the G/A genotype of the BDNF G196A polymorphism was associated with a significantly better therapeutic effect in the MADRS scores during this study. When milnacipran and fluvoxamine-treated subjects were analysed independently, the G/A genotype group showed greater reduction of MADRS scores than other genotype groups, irrespective of which antidepressant was administered. These results suggest that the BDNF G196A polymorphism in part determines the antidepressant effect of both milnacipran and fluvoxamine.

Adult↗

PubMed2006

The 2',3'-cyclic nucleotide 3'-phosphodiesterase and oligodendrocyte lineage transcription factor 2 genes do not appear to be associated with schizophrenia in the Japanese population.

Several lines of evidence suggest that disturbance of myelin-related genes is associated with the etiology of schizophrenia. Recently, the 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) gene and the oligodendrocyte lineage transcription factor 2 (OLIG2) gene were reported to be related to the development of schizophrenia, based on the results of genetic association and microarray studies. In the present study, no significant association with schizophrenia was observed by single-marker or haplotype analysis for 6 tag SNPs of these genes (759 cases, 757 controls). These findings suggest that CNP and OLIG2 are unlikely to be related to the development of schizophrenia in the Japanese population.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

PubMed2006

Impact of the DISC1 Ser704Cys polymorphism on risk for major depression, brain morphology and ERK signaling.

Disrupted-in-schizophrenia 1 (DISC1), identified in a pedigree with a familial psychosis with the chromosome translocation (1:11), is a putative susceptibility gene for psychoses such as schizophrenia and bipolar disorder. Although there are a number of patients with major depressive disorder (MDD) in the family members with the chromosome translocation, the possible association with MDD has not yet been studied. We therefore performed an association study of the DISC1 gene with MDD and schizophrenia. We found that Cys704 allele of the Ser704Cys single-nucleotide polymorphism (SNP) was associated with an increased risk of developing MDD (P=0.005, odds ratio=1.46) and stronger evidence for association in a multi-marker haplotype analysis containing this SNP (P=0.002). We also explored possible impact of Ser704Cys on brain morphology in healthy volunteers using MR imaging. We found a reduction in gray matter volume in cingulate cortex and a decreased fractional anisotropy in prefrontal white matter of individuals carrying the Cys704 allele compared with Ser/Ser704 subjects. In primary neuronal culture, knockdown of endogenous DISC1 protein by small interfering RNA resulted in the suppression of phosphorylation of ERK and Akt, whose signaling pathways are implicated in MDD. When effects of sDISC1 (Ser704) and cDISC1 (Cys704) proteins were examined separately, phosphorylation of ERK was greater in sDISC1 compared with cDISC1. A possible biological mechanism of MDD might be implicated by these convergent data that Cys704 DISC1 is associated with the lower biological activity on ERK signaling, reduced brain gray matter volume and an increased risk for MDD.

Adult↗

PubMed2006

Association analysis of delta-opioid receptor gene polymorphisms in methamphetamine dependence/psychosis.

The role of the delta-opioid receptor (OPRD1) in methamphetamine (MAP) addiction was investigated using association analysis between OPRD1 gene polymorphisms and MAP dependence/psychosis. DNA samples from Japanese patients with MAP dependence/psychosis were analyzed to find polymorphisms in OPRD1 gene exons and exon-intron boundaries. One novel single nucleotide polymorphism (SNP) in intron 1 and two SNPs in exon 3 were identified. The two SNPs in exon 3 were in linkage disequilibrium. No significant difference was observed in either genotypic or allelic frequencies of these SNPs between controls (n = 260) and MAP dependent/psychotic patients (n = 170). Global analyses using the three SNPs and subcategory analyses on clinical parameters also showed no significant differences. These results suggest that the OPRD1 gene variants may not be a factor in vulnerability to MAP dependence/psychosis.

Adult↗

PubMed2006

Association analysis of SOD2 variants with methamphetamine psychosis in Japanese and Taiwanese populations.

SOD2 (superoxide dismutase 2) plays a crucial role in protecting the cells against damage caused by free radicals, by catalyzing their detoxification. On the other hand, cell damage caused by free radical generation following methamphetamine administration has been postulated as one of the possible pathophysiological mechanisms for methamphetamine psychosis. Hence, we investigated the association of SOD2 polymorphisms with the development of methamphetamine psychosis, in two independent populations of Japan and Taiwan. We recruited 116 patients with methamphetamine psychosis and 189 controls in Japan, and 135 patients with methamphetamine psychosis and 204 controls in Taiwan. The methamphetamine group was divided into two clinical subtypes: a transient type of psychosis (i.e., good prognosis) and a prolonged type of psychosis (i.e., poor prognosis), according to the course of the manifestation of psychosis. With reference to the genotypic and allelic frequencies of Ala/Val functional polymorphism in exon 2, we found significant differences between individuals with prolonged methamphetamine psychosis and control samples from Japan and Taiwan in the genotypic (P value 0.014 and 0.016, respectively) and in the allelic (P value 0.004 and 0.047, respectively) frequencies. Our results suggest that Ala/Val polymorphism of the SOD2 gene could be associated with the risk of developing methamphetamine psychosis.

Adolescent↗

PubMed2006

Genetic variant of prodynorphin gene is risk factor for methamphetamine dependence.

Previous studies have indicated that genetic factors substantially affect development of substance use disorders, including methamphetamine dependence. Prodynorphin (PDYN) is an opioid peptide precursor that yields dynorphins, endogenous kappa opioid-receptor agonists that play important roles in substance abuse. A physiologically active polymorphism of 1-4 repeats of a 68-bp element in the promoter region of the PDYN gene has been identified. We analyzed this polymorphism of the PDYN gene by a case-control association study in 143 patients with methamphetamine dependence and 209 healthy controls in the Japanese population. A 3- or 4-repeat allele in the PDYN gene promoter was found significantly more frequently in patients with methamphetamine dependence than in controls (chi(2)=9.45, p=0.0021). A 3- or 4-repeat allele in the PDYN gene promoter, which was shown to produce significantly higher transcription activity of the PDYN gene than a 1- or 2-repeat allele, is a genetic risk factor for development of methamphetamine dependence (odds ratio: 1.83, 95% CI=1.24-2.68).

Adult↗

PubMed2006

Association between chromogranin A gene polymorphism and schizophrenia in the Japanese population.

It has been reported that expression of the chromogranin A (CHGA) gene is reduced in the prefrontal cortex and cerebrospinal fluid of patients with schizophrenia. Single-marker and haplotype analyses of SNPs within the CHGA gene were performed in 633 subjects with schizophrenia and 589 healthy controls. A significant association with schizophrenia was observed to one SNP marker, rs9658635 (p=0.0269), and with a 2 marker haplotype (p=0.0016). Significant association of rs9658635 was then replicated in a second independent cohort (377 schizophrenia and 338 control samples) (p=0.007). These results suggest that the CHGA gene is associated with the risk of developing schizophrenia in the Japanese population.

Adult↗

PubMed2006

No association of complexin1 and complexin2 genes with schizophrenia in a Japanese population.

Several investigations suggest that complexin may be a schizophrenia-susceptibility factor. We conducted a genetic association analysis between complexin genes (CPLX1 and CPLX2) and schizophrenia in Japanese patients (377 cases and 341 controls). Ten and eleven haplotype-tagging (ht)SNPs in CPLX1 and CPLX2, respectively, were selected. Only one htSNP (rs930047 in CPLX2) in allele-wise analysis showed significance, and even this disappeared with an increased sample size (563 cases and 519 controls: P = .757). Haplotype-wise analysis showed a weak association with a combination of htSNPs in CPLX2 (P = .0424), but this may be a result of type I error due to multiple testing. Our results suggest that complexin genes do not play a major role in schizophrenia in Japanese patients.

Adaptor Proteins, Vesicular Transport↗

PubMed2006

Disability and patient's appraisal of general health contribute to depressed mood in rheumatoid arthritis in a large clinical study in Japan.

The aim of this study was to evaluate the factors responsible for depressed mood in rheumatoid arthritis (RA). Clinical and laboratory measures were collected from 4558 RA patients enrolled in a large clinical cohort study for RA conducted at the Institute of Rheumatology, Tokyo Women's Medical University (IORRA study). A two-question depressed screening included in the U.S. Preventive Services Task Force recommendation were utilized to identify "depressed patients." A total of 1875 (41.1%) were identified as "depressed patients" who presented with symptoms suggestive of depression. Patient's Visual Analog Scale (VAS) for general health (43.3 mm vs 24.6 mm, P < 0.0001) and pain (40.9 mm vs 23.8 mm, P < 0.0001) and the disability index scores measured by the Health Association Questionnaire (HAQ) (0.986 vs 0.574, P < 0.0001) were significantly higher in depressed patients than in nondepressed patients. The presence of three or more comorbidities (odds ratio [OR] 2.157, P < 0.0001), infection (OR 1.754, P < 0.0001), and joint surgery (OR 1.878, P < 0.0001) were significantly correlated with depressed mood in RA. The results of the Generalized Linear Model analysis showed that HAQ disability index (P < 0.0001) and patient's VAS for general health (P < 0.0001) were also strongly and significantly associated to the response variable "probability of depressed patients." Patient appraisal of poor general health and greater disability were associated with depressed mood in RA.

Arthritis, Rheumatoid↗

PubMed2006

Positive association of the serotonin 5-HT7 receptor gene with schizophrenia in a Japanese population.

Several lines of evidence suggest that abnormalities in the serotonin system may be related to the pathophysiology of schizophrenia. The 5-HT7 receptor is considered to be a possible schizophrenia-susceptibility factor, based on findings from binding, animal, postmortem, and genomewide linkage studies. In this study, we conducted linkage disequilibrium (LD) mapping of the human 5-HT7 receptor gene (HTR7) and selected four 'haplotype-tagging (ht) SNPs'. Using these four htSNPs, we then conducted an LD case-control association analysis in 383 Japanese schizophrenia patients and 351 controls. Two htSNPs (SNP2 and SNP5) and haplotypes were found to be associated with schizophrenia. A promoter SNP (SNP2) was further assessed in a dual-luciferase reporter assay, but it was not found to have any functional relevance. Although we failed to find an actual susceptibility variant that could modify the function of HTR7, our results support the supposition that HTR7 is a susceptibility gene for schizophrenia in this ethnic group.

Adult↗

PubMed2006

Lithium response and Val66Met polymorphism of the brain-derived neurotrophic factor gene in Japanese patients with bipolar disorder.

Lithium is a first-line agent for the treatment of bipolar disorder. A significant association between the Val66Met polymorphism of the brain-derived neurotrophic factor gene and bipolar disorder has been reported. We investigated whether this polymorphism is associated with the response to lithium treatment in Japanese patients with bipolar disorder. Patients had been treated with lithium carbonate for more than 1 year, and the response was retrospectively evaluated. No significant differences were found in the genotype distribution or allele frequency between responders and non-responders. Our results suggested that the brain-derived neurotrophic factor Val66Met polymorphism might not greatly contribute to the efficacy of lithium in bipolar disorder.

Adult↗

PubMed2006

An association study between catechol-O-methyl transferase gene polymorphism and methamphetamine psychotic disorder.

OBJECTIVE: A series of methamphetamine psychosis reveals two kinds of clinical courses of methamphetamine psychosis: transient type and prolonged type. Furthermore, paranoid psychosis sometimes recurs without methamphetamine reuse, referred to as spontaneous relapse. Dysfunction of central dopaminergic neurotransmission has been implicated in the pathogenesis of these psychiatric states. Catechol-O-methyl transferase appears to play a unique role in regulating synaptic dopaminergic activity. This study aimed to investigate whether a functional polymorphism of the catechol-O-methyl transferase gene would be involved in the development of these psychiatric states. BASIC METHODS: We examined the functional polymorphism of val 158 met (catechol-O-methyl transferase) in 143 patients with methamphetamine psychosis and 200 healthy controls in Japan. The patients were divided into subgroups by several characteristic clinical features. MAIN RESULTS: We found a significant difference in the catechol-O-methyl transferase allele frequency between patients with spontaneous relapse and the controls (P=0.018, odds ratio=1.67). Odds ratio implied that the patients with spontaneous relapse had a nearly 1.7-fold higher rate of the low activity alleles (met) than the controls. CONCLUSIONS: Our results indicate that the met allele frequency of the catechol-O-methyl transferase is associated with patients who experienced methamphetamine psychosis and spontaneous relapse, suggesting that patients with a met allele appear to be at increased risk of an adverse response to methamphetamine.

Adult↗

PubMed2006

Association between gene polymorphisms of SLC22A3 and methamphetamine use disorder.

BACKGROUND: Methamphetamine (MAP) is one of the most frequently used illegal substances in Japan, and family and twin studies have suggested that genetic factors contribute to psychostimulant dependence, including MAP dependence. Organic cation transporter 3 (OCT3) has been reported to be involved in the disposition of MAP as well as MAP-induced behavioral changes in animals. Moreover, SLC22A3 (which encodes OCT3) is a candidate gene for MAP dependence because it is located within a chromosomal region associated with substance dependence. METHODS: Using 96 healthy control subjects, linkage disequilibrium (LD) within the SLC22A3 was investigated, and 5 single-nucleotide polymorphisms (SNPs) were selected as haplotype tag SNPs to search for an association with MAP dependence. Single-marker analyses and haplotype analyses of these SNPs were performed in 213 subjects with MAP dependence and 443 healthy controls. RESULTS: SLC22A3 polymorphisms were not significantly associated with MAP dependence in any of the single-marker and haplotype analyses. When subjects with MAP dependence were divided into polysubstance and single-MAP users, genotype and allele frequency of SNP2 (p=0.024, p=0.011, respectively), allele frequency of SNP3 (p=0.037), and haplotypic frequencies for these 2 SNPs (p=0.0438) differed significantly between groups. CONCLUSIONS: These results suggest that polymorphisms of SLC22A3 are related to the development of polysubstance use in Japanese patients with MAP dependence.

Adult↗