The functional analysis by structural change of Chromogranin in the neuropsychiatric diseases.

科学研究費助成事業(科学研究費補助金)研究成果報告書：研究活動スタート支援2010-2011課題番号：２２８９００２

Association study of the vesicular monoamine transporter 1 (VMAT1) gene with schizophrenia in a Japanese population

BACKGROUND: Vesicular monoamine transporters (VMATs) mediate accumulation of monoamines such as serotonin, dopamine, adrenaline, and noradrenaline from the cytoplasm into storage organelles. The VMAT1 (alternatively solute carrier family 18: SLC18A1) regulates such biogenic amines in neuroendocrine systems. The VMAT1 gene maps to chromosome 8p21.3, a locus with strong evidence of linkage with schizophrenia. A recent study reported that a non-synonymous single nucleotide polymorphism (SNP) of the gene (Pro4Thr) was associated with schizophrenia. METHODS: We attempted to replicate this finding in a Japanese sample of 354 schizophrenics and 365 controls. In addition, we examined 3 other non-synonymous SNPs (Thr98Ser, Thr136Ile, and Val392Leu). Genotyping was performed by the TaqMan allelic discrimination assay. RESULTS: There was no significant difference in genotype or allele distribution of the three SNPs of Pro4Thr, Thr136Ile, or Val392Leu between patients and controls. There was, however, a significant difference in genotype and allele distributions for the Thr98Ser polymorphism between the two groups (P = 0.01 for genotype and allele). When sexes were examined separately, significant differences were observed in females (P = 0.006 for genotype, P = 0.003 for allele), but not in males. The Thr98 allele was more common in female patients than in female controls (odds ratio 1.69, 95% CI 1.19–2.40, P = 0.003). Haplotype-based analyses also provided evidence for a significant association in females. CONCLUSION: We failed to replicate the previously reported association of Pro4Thr of the VMAT1 gene with schizophrenia. However, we obtained evidence for a possible role of the Thr98Ser in giving susceptibility to schizophrenia in women

Possible association between Interleukin-1beta gene and schizophrenia in a Japanese population

Background: Several lines of evidence have implicated the pro-inflammatory cytokine interleukin-1beta (IL-1 beta) in the etiology of schizophrenia. Although a number of genetic association studies have been reported, very few have systematically examined gene-wide tagging polymorphisms. Methods: A total of 533 patients with schizophrenia (302 males: mean age +/- standard deviation 43.4 +/- 13.0 years; 233 females; mean age 44.8 +/- 15.3 years) and 1136 healthy controls (388 males: mean age 44.6 +/- 17.3 years; 748 females; 46.3 +/- 15.6 years) were recruited for this study. All subjects were biologically unrelated Japanese individuals. Five tagging polymorphisms of IL-1 beta gene (rs2853550, rs1143634, rs1143633, rs1143630, rs16944) were examined for association with schizophrenia. Results: Significant difference in allele distribution was found between patients with schizophrenia and controls for rs1143633 (P = 0.0089). When the analysis was performed separately in each gender, significant difference between patients and controls in allele distribution of rs1143633 was observed in females (P = 0.0073). A trend towards association was also found between rs16944 and female patients with schizophrenia (P = 0.032). Conclusions: The present study shows the first evidence that the IL-1 beta gene polymorphism rs1143633 is associated with schizophrenia susceptibility in a Japanese population. The results suggest the possibility that the influence of IL-1 beta gene variations on susceptibility to schizophrenia may be greater in females than in males. Findings of the present study provide further support for the role of IL-1 beta in the etiology of schizophrenia

Modulation of cortisol responses to the DEX/CRH test by polymorphisms of the interleukin-1beta gene in healthy adults

<p>Abstract</p> <p>Background</p> <p>Recently, hypothalamus-pituitary-adrenal (HPA) axis function assessed with the combined dexamethasone (DEX)/corticotropin releasing hormone (CRH) test has been shown to be associated with response to antidepressant treatment. A polymorphism (rs16944) in the interleukin-1beta (<it>IL-1β</it>) gene has also been reported to be associated with the medication response in depression. These findings prompted us to examine the possible association between <it>IL-1β </it>gene polymorphisms and HPA axis function assessed with the DEX/CRH test.</p> <p>Methods</p> <p>DEX/CRH test was performed in 179 healthy volunteers (45 males: mean age 40.5 ± 15.8 years; 134 females: mean age 47.1 ± 13.2 years). Five tagging single nucleotide polymorphisms (SNPs) of <it>IL-1β </it>gene (rs2853550, rs1143634, rs1143633, rs1143630, rs16944) were selected at an r²threshold of 0.80 with a minor allele frequency > 0.1. Genotyping was performed by the TaqMan allelic discrimination assay. A two-way factorial analysis of variance (ANOVA) was performed with the DEX/CRH test results as the dependent variable and genotype and gender as independent variables. To account for multiple testing, <it>P </it>values < 0.01 were considered statistically significant for associations between the genotypes and the cortisol levels.</p> <p>Results</p> <p>The cortisol levels after DEX administration (DST-Cortisol) showed significant associations with the genotypes of rs16944 (<it>P </it>= 0.00049) and rs1143633 (<it>P </it>= 0.0060), with no significant gender effect or genotype × gender interaction. On the other hand, cortisol levels after CRH administration (DEX/CRH-Cortisol) were affected by gender but were not significantly influenced by the genotype of the examined SNPs, with no significant genotype × gender interaction.</p> <p>Conclusions</p> <p>Our results suggest that genetic variations in the <it>IL-1β </it>gene contribute to the HPA axis alteration assessed by DST-Cortisol in healthy subjects. On the other hand, no significant associations of the <it>IL-1β </it>gene polymorphisms with the DEX/CRH-Cortisol were observed. Confirmation of our findings in futures studies may add new insight into the communication between the immune system and the HPA axis.</p

Is the 7/2^<->_<1> isomer state of ^<43>S spherical?

We report on the spectroscopic quadrupole moment measurement of the 7/2−1 isomeric state in S271643 [E∗=320.5(5)  keV, T1/2=415(3)  ns], using the time dependent perturbed angular distribution technique at the RIKEN RIBF facility. Our value, ∣Qs∣=23(3)  efm2, is larger than that expected for a single-particle state. Shell model calculations using the modern SDPF-U interaction for this mass region reproduce remarkably well the measured ∣Qs∣, and show that non-negligible correlations drive the isomeric state away from a purely spherical shape

コガタ クライオサンプラー ヲ モチイタ ショウワキチ デノ セイソウケン タイキ サイシュ ジッケン ダイ49ジタイ ジッケン ホウコク

第49次南極地域観測隊(第49次隊)夏期間に昭和基地において,新たに開発した小型クライオサンプラーを用いた成層圏大気採取実験を実施した.小型クライオサンプラーは高圧ネオンガスを断熱膨張させて液体ネオンを製造し,希薄な成層圏大気を固化・液化採取するものであり,既存の大型サンプラーが必要とした液体ヘリウムが不要であること,小型軽量であるために満膨張時容積1000-2000 m3の小型プラスチック気球を用いて成層圏まで飛揚させることが可能であるという特徴がある.2007年12月30日と2008年1月4日に計4機の小型サンプラーを放球し,すべて回収に成功した.そのうち,2機は高度18 km及び25kmの成層圏大気の採取に成功した.採取された大気試料は国内に持ち帰られた後,各種温室効果気体濃度と同位体比の分析が行われた.As a part of summer observations of the 49th Japanese Antarctic Research Expedition, stratospheric whole air sampling experiments were conducted at Syowa Station using newly developed compact cryogenic air samplers. The compact sampler uses liquefied neon (produced in-situ) as a refrigerant to solidify or liquefy atmospheric constituents. Because of its reduced size and weight, the sampler can be launched using small-size balloons (1000&#8211;2000 m3 in volume). On December 30, 2007 and January 4, 2008, a total of 4 samplers were launched from Syowa Station and recovered on the same day as their launches. Two of them functioned as designed and collected stratospheric air samples at altitudes of 18 and 25 km. The air samples were analyzed for greenhouse gas concentrations and stable isotopes after return to Japan