2002 Fiscal Year Final Research Report Summary
PHARMACOGENETICS RESEARCH AND MUTATION SEARCH FOR THE SENSITIVITY OF BENZODIAZEPINE DRUGS
| Project/Area Number |
13671036
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Fujita Health University |
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Principal Investigator |
NAKAO Iwata FUJITA HEALTH UNIV., SCHOOL (PSYCHITRY)ASSO. PROFESSOR, 医学部・精神医学講座, 助教授 (60312112)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Benzidiazepine / GABA receptor / Pharmacogenetics / Schizophrenia / GENETIC VARIANTS |
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| 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.
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