PubMed Health⌕ Search

Biomedical subjects

Hiroyuki Hibino

Publications and source records attributed to Hiroyuki Hibino.

16 recordsLinked to original sources

Association study between the TNXB locus and schizophrenia in a Japanese population.

The chromosome 6p21-24 region, which contains the human leukocyte antigen (HLA) region, has been suggested as an important locus for a susceptibility gene for schizophrenia. Recently, a significant association between schizophrenia and the TNXB locus, located immediately telomeric of the NOTCH4 locus in the HLA region, was observed. Few studies have further investigated the region in schizophrenia. In the present study, we investigated the region in a Japanese population. Subjects included 241 patients with schizophrenia and 290 controls. Twenty-six single nucleotide polymorphisms (SNPs) and the corresponding haplotypes were analyzed. As a result, exactly the same SNPs in the TNXB locus (rs1009382 and rs204887) as in the previous study were associated with schizophrenia (P = 0.034 and 0.034, respectively, uncorrected). A SNP (rs2071287) in the NOTCH4 locus and haplotype around it were also suggested to associate with the disease, consistent with another previous study (P = 0.041 and permutation P = 0.024, respectively, uncorrected). Although these associations became insignificant after Bonferroni correction, the findings might provide support for the association of the TNXB locus or its adjacent region of the NOTCH4 locus with schizophrenia.

Adult↗

No association of DRD2, DRD3, and tyrosine hydroxylase gene polymorphisms with personality traits in the Japanese population.

BACKGROUND: Dopamine D2 receptor (DRD2) and dopamine D3 receptor (DRD3) genes could be candidates for personality-related genes considering their pharmacological profiles or structures. However, a limited number of studies have investigated the association between these genes and personality traits. In the present study, we investigated the DRD2, DRD3, and tyrosine hydroxylase (TH) genes in relation to personality traits in the Japanese population. Epistasis (gene-gene interaction) among the genes was extensively analyzed, in addition to the analysis based on each gene. METHODS: The -241A/G, -141C Ins/Del, and Ser311Cys polymorphisms in the DRD2 gene, the Ser9Gly polymorphism of the DRD3 gene, and the Val81Met and PstI site polymorphisms in the TH gene were genotyped in 257 healthy Japanese subjects. Personality traits were evaluated by using the Revised NEO Personality Inventory (NEO PI-R) and the State-Trait Anxiety Inventory (STAI). The associations between gene polymorphisms and the scores for NEO PI-R or Trait Anxiety of STAI were statistically analyzed by one-way analysis of covariance (ANCOVA) adjusting sex and age. Epistasis was assessed using two-way ANCOVA between the polymorphisms of independent two genes. RESULTS: In the analysis based on each gene, trends for association were observed between State Anxiety and the DRD2 -141C Ins/Del polymorphism (p = 0.031, uncorrected), and between Trait Anxiety and the DRD2 Ser311Cys or TH PstI site polymorphism (p = 0.048 and 0.041, respectively, uncorrected). In epistatic analysis, a trend for interaction was observed on the scores for Neuroticism and Trait Anxiety between the DRD2 -141C Ins/Del and TH Val81Met polymorphisms (p = 0.015 and 0.010, respectively, uncorrected). However, these differences were insignificant after Bonferroni correction. CONCLUSION: The present study did not provide evidence for the association between these dopamine-related genes and personality traits in the Japanese population.

Journal Article↗

Association study of the dysbindin (DTNBP1) gene in schizophrenia from the Japanese population.

Dysbindin (DTNBP1: dystrobrevin binding protein 1), located on 6p22.3, is a candidate susceptibility gene for schizophrenia. Several studies, mostly in Caucasians, have provided evidence for an association between schizophrenia and the gene, although no common polymorphism or haploytpe has been established. In Asian populations, two studies investigated a limited number of single nucleotide polymorphisms (SNPs) of dysbindin and observed support for the association. In the present study, we investigated 12 SNPs of dysbindin, including those examined in previous Asian studies, and the corresponding haplotypes in a Japanese people with schizophrenia. As a result, no significant difference was observed between patients and controls in allelic frequencies or genotypic distributions of the 12 SNPs. Permutation test however showed significant differences in frequencies of the estimated 10-marker haplotypes between patients and controls (global p = 0.006). The present study may provide further support for an association between dysbindin and schizophrenia in Asian populations. The results might be similar to a previous Asian study, but specific haplotypes suggested for the association differed between the studies. Studies with more markers and subjects may be required before firm conclusions can be reached.

Adult↗

No association between the Clara cell secretory protein (CC16) gene polymorphism and personality traits.

Clara cell secretory protein (CC16) is an anti-inflammatory protein expressed in the respiratory tract. Several studies have suggested the association between CC16 and mental disturbances, such as schizophrenia, depression, and post-traumatic stress disorder. In the present study, we investigated the association between the CC16 gene A38G polymorphism and personality traits in 214 healthy Japanese subjects. Personality traits were evaluated by using the Revised NEO Personality Inventory (NEO PI-R) and the State-Trait Anxiety Inventory (STAI). As a result, no significant association was observed between the genotypes and the scores of the NEO PI-R or the STAI. The present results suggest that CC16 may not have a major role in the development of personality traits.

Adult↗

No association of 5-HT2C, 5-HT6, and tryptophan hydroxylase-1 gene polymorphisms with personality traits in the Japanese population.

Serotonin 2C receptor (5-HT(2C)), serotonin 6 receptor (5-HT(6)), and tryptophan hydroxylase-1 (TPH1) genes could be candidates for personality-related genes considering the role of serotonin in various mental functions and behavior. However, a limited number of studies have investigated the association between these genes and personality traits. In the present study, we investigated the three serotonin-related genes, 5-HT(2C), 5-HT(6), and TPH1 genes, in relation to personality traits in the Japanese population. The Cys23Ser polymorphisms in the 5-HT(2C) gene, the 267T/C polymorphism of the 5-HT(6) gene, and the 779A/C polymorphisms in the TPH1 gene were genotyped in 253 healthy Japanese subjects. Personality traits were evaluated by using the Revised NEO Personality Inventory (NEO PI-R) and the State-Trait Anxiety Inventory (STAI). As a result, no significant association was observed between the polymorphisms and the NEO PI-R or the STAI scores. The present results did not provide evidence for the association between the three serotonin-related genes and personality traits. The genes might not have major role in the development of personality traits, although further investigation with larger sample size may be recommended for conclusion.

Adult↗

Association between dopamine D4 receptor (DRD4) exon III polymorphism and Neuroticism in the Japanese population.

The association between the dopamine D4 receptor (DRD4) exon III polymorphism and personality trait of novelty seeking (NS) has been studied intensively. In the Japanese population, the results of the previous studies did not always coincide. In the present study, we investigated the association between the polymorphism and personality traits evaluated by using the Revised NEO Personality Inventory (NEO PI-R) and State-Trait Anxiety Inventory (STAI) in 196 Japanese subjects. A meta-analysis of the present and previous Japanese studies was also conducted regarding NS. As a result, significant association was observed between the polymorphism and personality traits evaluated by using NEO PI-R as a whole (p=0.022, MANCOVA). Subsequent analyses showed a significant association between short alleles (2-4 repeats) and higher scores for Neuroticism or its subscales, Anxiety, Depression, and Vulnerability (p=0.015, 0.039, 0.021, and 0.008, respectively, uncorrected). No other significant difference in the scores for NEO PI-R was observed in the subsequent analyses. Significant association was also observed between the polymorphism and scores for STAI as a whole (p=0.004, MANCOVA). Subsequent analyses did not show significant association, although a weak trend for the relation between the genotype consisting of short alleles and Trait Anxiety was observed (p=0.10, uncorrected). The meta-analysis showed no significant association between the polymorphism and NS. Thus, the present study suggested the association between the short allele of the DRD4 exon III polymorphism and personality trait of Neuroticism in Japanese subjects.

Adult↗

Association between corticotropin-releasing hormone receptor 2 (CRHR2) gene polymorphism and personality traits.

Corticotropin-releasing hormone (CRH) has been implicated in the pathophysiology of anxiety disorders and depression. Corticotropin-releasing hormone receptor 2 (CRHR2) is one of the receptors that mediate CRH signal. The purpose of the present study was to investigate the association between the CRHR2 gene and personality traits, evaluated using the Revised NEO Personality Inventory (NEO PI-R), in 243 healthy Japanese subjects. As a result, significant association was observed between the polymorphism in intron 2 (rs2267717) and Openness (P = 0.004, uncorrected, anova), while no relationship was observed concerning Neuroticism. The present result suggests an association between CRHR2 and the personality trait of Openness.

Adult↗

Combined analysis of association between personality traits and three functional polymorphisms in the tyrosine hydroxylase, monoamine oxidase A, and catechol-O-methyltransferase genes.

Several molecular genetic studies have been conducted with regard to the association between catecholamine-related genes and personality traits. However, the results of replication studies did not always coincide. One of the possible reasons may be that the effect exerted by the individual gene is small. In the present study, we investigated the association between personality traits and systematic combination of functional polymorphisms in three genes that regulate the metabolism of catecholamines, namely, tyrosine hydroxylase (TH), monoamine oxidase A (MAOA), and catechol-O-methyltransferase (COMT). The (TCAT)n repeat in the TH gene, the promoter variable number tandem repeat (VNTR) in the MAOA gene, and Val158Met in the COMT gene were genotyped in 256 healthy Japanese volunteers. Personality traits were evaluated using the NEO Personality Inventory-Revised (NEO PI-R). As a result, the score for Neuroticism increased, and those for Extraversion and Conscientiousness decreased according to the degree of functional polymorphic change, i.e., the lower synthesis/higher catalysis of catecholamines. A statistically significant difference was observed in the change of Extraversion (p=0.04, after Bonferroni correction). These results may provide evidence for the association between metabolic change of catecholamines and personality traits, which may be due to the additive effect of the three genes.

Adult↗

Seasonality of schizophrenia births in the Japanese population: increased winter births possibly confined to the north area.

A number of North American and European studies have observed a higher proportion of winter births in schizophrenia patients. Thus, seasonal fluctuation of unknown environmental factors may affect brain development in ways that alter susceptibility to schizophrenia. Specification of these factors may help elucidate the etiopathological mechanism of the disease, about which little is certain. A small number of studies have investigated this issue in Asian populations, and the findings are not as consistent as those of Western populations. No remarkable excess of winter births has been observed in Japanese or Korean studies, while some studies have reported a significant decrease of summer births. We further investigated the issue in Japanese patients with schizophrenia (n=3927). No significant excess of winter births was observed, but a decrease in the summer births was found in male subjects. This is largely consistent with previous Japanese studies; however, when the subjects were confined to those born in a colder and higher latitude area of Japan (n=1338), a consistent trend for both a winter increase, and a summer decrease, was found. However, the results did not consistently reach statistical significance, possibly due to the lack of statistical power. Environmental factors that correlate with latitude might play a role in the development of the seasonality of births in schizophrenia. Further studies in a larger sample size are required to test these possibilities.

Catchment Area, Health↗

Serotonin 2A receptor gene polymorphism and personality traits: no evidence for significant association.

A number of studies have observed associations between the serotonin 2A (5-HT2A) receptor and mental disorders. Here, we investigated correlations between polymorphisms (-1438G/A and 102T/C) of the 5-HT2A gene and personality traits in healthy Japanese volunteers (n = 239). The personality traits were evaluated using the Revised NEO Personality Inventory (NEO PI-R). The -1438G/A and 102T/C were in complete linkage disequilibrium. There was a tendency for associations between the genotype and the scores for Agreeableness, Conscientiousness and Neuroticism of the NEO PI-R (P = 0.028, 0.039 and 0.062, respectively; analysis of variance, uncorrected for multiple testing). Subjects with the A/A of -1438G/A (or T/T of 102T/C) appeared to be lower in Neuroticism and higher in Conscientiousness than the rest of the subjects. However, the results were statistically non-significant after Bonferroni's correction for multiple testing of the five scales of the NEO PI-R. Thus, the present study provided no evidence for statistically significant associations between the 5-HT2A polymorphisms and the personality traits.

Adult↗

Season of birth effect on personality in a general population.

Seasonality of births in schizophrenia and other mental disorders has been consistently observed. This may be through effects of unknown environmental factors that seasonally fluctuate on the brain development. The effects may affect cognitive function of the brain and behavioral characteristics that might be correlated with the development of personality not only in patients with mental disorders but also in healthy subjects. We, therefore, investigated the effects of season of birth on personality traits in healthy Japanese adults (n = 397). Personality traits were evaluated using the NEO Personality Inventory-Revised (NEO PI-R). A trend for lower Agreeableness in subjects born during winter (December to February) than other subjects was observed (P = 0.036, after correction for the multiple testing, multiple regression analysis adjusting for age and sex). Other major factors of the NEO PI-R, including Neuroticism, Extraversion, Openness and Conscientiousness, were not affected by season of birth. Further studies may be recommended to confirm the results, considering the relatively limited sample size. Evaluation of cognitive functions and behaviors using other measures including event-related potentials and functional MRI may also help the interpretation of the present result.

Adult↗

Mitochondrial DNA polymorphisms and extraversion.

Mitochondria is the major site of energy production in cells, therefore, mitochondrial abnormality may affect functions of organs including the brain, which constantly requires high levels of energy consumption. Previous studies have suggested a role of mitochondria and their DNA polymorphisms in neuro-psychiatric disorders, including Alzheimer's disease, Parkinson's disease, schizophrenia and bipolar mood disorder. Thus, we hypothesized that mitochondrial DNA polymorphisms might be related with the development of personality. The present study investigated a role of two mitochondrial DNA polymorphisms, the C5178A and A10398G, in personality traits evaluated using the NEO PI-R scores in 238 healthy Japanese volunteers. Subjects with the 5178A genotype showed significantly higher extraversion score than those with the 5178C genotype (P = 0.027), while no significant association was observed between the C5178A polymorphism and other scores. No significant association was found between the A10398G polymorphism and any scores. Regarding the 5178-10398 haplotype, the score of extraversion, not other scores, was significantly associated with the A-G haplotype (P = 0.042). Although further studies are recommended for the confirmation, the result may suggest a role of the mitochondrial DNA polymorphism in the personality trait.

Adult↗

Association of six polymorphisms of the NOTCH4 gene with schizophrenia in the Japanese population.

The NOTCH4 gene is located at 6p21.3 and involved in the development and patterning of the central nervous systems. Recently, Wei and Hemmings [2000] observed that the gene was associated with schizophrenia. Subsequent to the report, several studies investigated the gene in schizophrenia, with controversial and inconclusive results. In the present study, we investigated six polymorphisms (SNPs 1-5 and a CTG repeat) of the gene in Japanese subjects with schizophrenia (n = 284) and the same number of controls. The polymorphisms include SNP5, which has been observed to be associated with schizophrenia in a Chinese population and two new SNPs 3-4 adjacent to SNP5, in addition to the SNPs 1-2 and the CTG repeat, which were suggested for the association with the disease in the previous study. As a result, no significant difference in genotypic distributions or allelic frequencies of the six polymorphisms of the gene was observed between the patients and the controls. Also, no significant difference was found in frequencies of haplotypes of the six polymorphisms between the patients and the controls. However, the distribution of SNP2 was significantly deviated from Hardy-Weinberg equilibrium in the patients (P = 0.000986), not in the controls, which could be a chance or due to an association of SNP2 with the disease. In conclusion, the present study provided no clear evidence for an association between the NOTCH4 gene and schizophrenia in the Japanese population.

Adult↗

Serotonin transporter-linked promoter region polymorphism and personality traits in a Japanese population.

Serotonin transporter gene may play a critical role in a regulation of mood and other aspects of mental status. A large number of association studies have investigated a correlation between the polymorphism in the serotonin transporter-linked promoter region (5-HTTLPR) and anxiety-related personality traits. The results, however, have been inconsistent. Heterogeneity of subjects regarding gender, occupation, social-class and other environmental factors, in addition to effects of other genes, might have confounded the results. Here, we studied an association between the 5-HTTLPR polymorphism and personality traits in primarily female (78%) healthy subjects (n=244), who had homogeneous backgrounds regarding ethnicity (Japanese) and occupation. Personality traits of the subjects were assessed with the revised NEO Personality Inventory. No significant association was observed between the polymorphism and neuroticism or other personality traits, in all subjects, all females (n=190) or female nurses (n=159). Thus, our findings provided no evidence for an association between the 5-HTTLPR polymorphism and anxiety-related or other personality traits.

Adult↗

Human leukocyte antigen-A specificities and its relation with season of birth in Japanese patients with schizophrenia.

Several studies, including one from Japan, have observed an increase of Human Leukocyte Antigen (HLA)-A24 and A26 in schizophrenia, although others failed to observe the increase. No use of systematic diagnostic criteria and a not-adequately reliable typing technique might have affected the results in the previous studies. We investigated HLA-A specificities in Japanese patients with schizophrenia (DSM-IV), recruited from the same area as in the early Japanese study. A DNA-based technique (polymerase chain reaction-microtiter plate hybridization) was employed. No significant difference was observed in frequencies of any HLA-A specificities between patients and controls, including A24 and A26. No significant association was found between the HLA-A and birth-season in patients. Thus, no evidence was obtained for an association between HLA-A and schizophrenia from the Japanese population.

Adult↗

Sequence changes in six variants of rice tungro bacilliform virus and their phylogenetic relationships.

The DNA of three biological variants, G1, Ic and G2, which originated from the same greenhouse isolate of rice tungro bacilliform virus (RTBV) at the International Rice Research Institute (IRRI), was cloned and sequenced. Comparison of the sequences revealed small differences in genome sizes. The variants were between 95 and 99% identical at the nucleotide and amino acid levels. Alignment of the three genome sequences with those of three published RTBV sequences (Phi-1, Phi-2 and Phi-3) revealed numerous nucleotide substitutions and some insertions and deletions. The published RTBV sequences originated from the same greenhouse isolate at IRRI 20, 11 and 9 years ago. All open reading frames (ORFs) and known functional domains were conserved across the six variants. The cysteine-rich region of ORF3 showed the greatest variation. When the six DNA sequences from IRRI were compared with that of an isolate from Malaysia (Serdang), similar changes were observed in the cysteine-rich region in addition to other nucleotide substitutions and deletions across the genome. The aligned nucleotide sequences of the IRRI variants and Serdang were used to analyse phylogenetic relationships by the bootstrapped parsimony, distance and maximum-likelihood methods. The isolates clustered in three groups: Serdang alone; Ic and G1; and Phi-1, Phi-2, Phi-3 and G2. The distribution of phylogenetically informative residues in the IRRI sequences shared with the Serdang sequence and the differing tree topologies for segments of the genome suggested that recombination, as well as substitutions and insertions or deletions, has played a role in the evolution of RTBV variants. The significance and implications of these evolutionary forces are discussed in comparison with badnaviruses and caulimoviruses.

Amino Acid Sequence↗