1994 Fiscal Year Final Research Report Summary
LINKAGESTUDIES ON FAMILIES WITH MULTIPLE MEMBERS OF SCHIZOPHRENIA
| Project/Area Number |
05670827
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Psychiatric science
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| Research Institution | TOHO UNIVERSITY |
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Principal Investigator |
NAKAMURA Michiko Toho Uuniversity School of Medicine, Assistant Professor, 医学部, 講師 (50180401)
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| Co-Investigator(Kenkyū-buntansha) |
HEMMI Hiromichi Toho University School of Medicine, Associate professor, 医学部, 助教授 (90165514)
SUZUKI Jiro Toho University School of Medicine, professor&Chairman, 医学部, 教授 (10090408)
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| Project Period (FY) |
1993 – 1994
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| Keywords | Dopamine D4 receptor / Association / Schizophrenia / Familial predispositions / Polymorphism / PCR |
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| Research Abstract |
The human dopamine D4 receptor contains a polymorphism within the putative third cytoplasmic loop of the protein. The polymorphism is characterized by a varying number of 48-bp repeats in the gene.
Pharmacological characterization has suggested that this receptor is the site through which the atypical neuroleptic clozapine exerts its antipsychotic action and that some polymorphic variants display different pharmacological properties. This polymorphism could underlie indivisual differences in susceptability to schizophrenia.
In 1995, we have developed a simple method to detect DRD4 polymorphism by polymerase chain reaction.Genomic DNA was isolated from whole blood and analyzed by PCR.
We have examined two groups of unrelated schizophrenic cases and 52 healthy controls to determine the frequency of different D4 alleles in these groups. One group (B+group) consisted of 55 schizophrenic cases who have other family members of schizophrenia. The other group (B-group) consisted of 47 schizophren
… More
ic cases who have no other family members of schizophrenia.
Statistically significant difference in the distribution of the alleles existed between the cases of B+group and controls.The frequencies of the alleles of the 4,5 and 6 fold repeats significantly increased in the B+group, and the frequency of the alleles of 2 fold repeat decreased in the B+group.
We also found statistically significant difference in the distribution of the alleles between the cases of B-group and controls. The frequency of the alleles of the 4 fold repeat significantly increased in the B-group.
When we compare the allelic distribution in the B+group to that in the B-group, we found statistically significant difference. The frequency of the alleles of the 5 fold repeat significantly increased in the B+group.
In our investigation possible associations were noted between the DRD4 alleles and schizophrenia with familial predispositions and also between the DRD4 alleles and schizophrenia without familial predispositions. Although the studies of Nanko S.(1993) and of Sommmer S.(1993) reported that the association between the DRD4 alleles and schizophrenia was unlikely, the result of our study indicates furtherinvestigaions on the relation between this polymorphism and schizophrenia are needed. Less
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