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PHARMACOGENETICS RESEARCH AND MUTATION SEARCH FOR THE SENSITIVITY OF BENZODIAZEPINE DRUGS

Research Project

Project/Area Number 13671036
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionFujita Health University

Principal Investigator

NAKAO Iwata  FUJITA HEALTH UNIV., SCHOOL (PSYCHITRY)ASSO. PROFESSOR, 医学部・精神医学講座, 助教授 (60312112)

Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsBenzidiazepine / GABA receptor / Pharmacogenetics / Schizophrenia / GENETIC VARIANTS / 薬理遺伝学 / 精神疾患 / SNPs
Research Abstract

Among 18 GABAA receptor subunits, gamma2 and alpha1 subunit were investigated in this project. Both of them are essential for the construction of the benzodiazepine binding site for GABA-benzodiazepine complex. Additionally, they are addressed as the candidate gene for schizophrenia. For gamma2 subunit, short form and long form variants are expressed in the central nerve system resulting in the alternative splicing. In the schizophrenic patients brain, the expression level of long form were decreased. For alpha1, the expression level are increased in the brain.
[subjects and methods]
288 schizophrenic patients and 288 normal control were recruited. After written informed consent, DNA were extracted from peripheral blood samples. Mutation search were performed using dHPLC methods and direct sequencing. PCR-RFLP and primer extension were done for genotyping. Haplotype-based case-control association study were performed.
[results and discussion]
In gamma2, 6 SNPs were identified. Three of them which had more than 5% allele frequencies were genotyped for haplotype analysis. There is no association between schizophrenia and gamma2 locus. In alpha1, 8 SNPs were identified. Dense haplotype map were constructed and used for haplotype analysis. However, there is no association with schizophrenia. Because we could not find any amino acid substitutions in the two genes, we could not evaluate the sensitivity for benzodiazepine. In conclusion, gamma2 and alpha1 GABAa receptor genes did not have any abundant variants in Japanese population.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Suzuki T, Iwata N, et al.: "Association of Novel Genetic Variants in Serotonin 5-HT4 Receptor Gene (HTR4) with Japanese Schizophrenia"Am. J. Med. Genet.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okada M, Iwata N, et al.: "Pepstatin A Induces the Microglial Extracellular Acidification Distinct from Aspartic Proteases Inhibition"Glia. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Noda M, Iwata N, et al.: "Rrecombinant human 5-HT_<5A> receptors stably expressed in C6 glioma cells couple to multiple signal transduction pathways"J. Neurochem.. 84. 222-232 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Suzuki T, Iwata N, et al: "Association of Novel Genetic Variants in the Serotonin 5-HT4 Receptor Gene (HTR4) with Japanese Schizophrenia"Am. J. Med. Genet.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okada M, Iwata N, et al: "Pepstatin A Induces the Microglial Extracellular Acidification Distinct from Aspartic Proteases Inhibition"Glia. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Noda M, Iwata N, et al: "Recombinant human 5-HT_<5A> receptors stably expressed in C6 glioma cells couple to multiple signal transduction pathways"J. Neurochem.. 84. 222-232 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Suzuki T, Iwata N, et al.: "Association of Novel Genetic Variants in the Serotonin 5-HT4 Receptor Gene (HTR4) with Japanese Schizophrenia"Am.J.Med.Genet.. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Okada M, Iwata N, et al.: "Pepstatin A Induces the Microglial Extracellular Acidification Distinct from Aspartic Proteases Inhibition"Glia. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Noda M, Iwata N, et al.: "Rrecombinant human 5-HT_<5A>, receptors stably expressed in C6 glioma cells couple to multiple signal transduction pathways"J.Neurochem.. 84. 222-232 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Iwata N, N.Ozaki, T.Inada, Goldman D: "Association of a 5-HT5A receptor polymorphism, Pro15Ser, to schizophrenia"Molecular Psychiatry. 6(2). 217-219 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Imamura K, Sawada M, Ozaki N, Naito H, Iwata N, et al.: "Activation mechanism of brain microglia in patients with diffuse neurofibrillary tangles with calcification : a comparison with Alzheimer disease"Alzheimer Dis Assoc Disord. 15(1). 45-50 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Iwata N, Vallejo RL, Virkkunen M, Long JC, Suzuki T, Ozaki N, et al.: "Evidence for linkage of genetic variants at the serotonin 2B receptor gene (HTR2B) with finnish alcoholism"Biological Psychiatry. 49S. 164S (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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