IMMUNOPHARMACOGENETICS OF SCHIZOPHRENIA
IMMUNOPHARMACOGENETICS OF SCHIZOPHRENIA
批准号:
3386843
负责人:
EDMOND J YUNIS
金额:
$30.66万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1992
资助国家:
美国
项目状态:
已结题
起止时间:
1992-09-30 至 1995-08-31
关键词:
Jewish MHC class I antigen MHC class II antigen alleles antipsychotic agents clozapine dopamine drug adverse effect fluphenazine genetic markers granulocytopenia histocompatibility typing human subject human therapy evaluation immunogenetics immunopharmacology interleukin 2 leukocyte activation /transformation major histocompatibility complex mental disorder chemotherapy pharmacogenetics polymerase chain reaction restriction fragment length polymorphism schizophrenia transferrin receptor
中文摘要
这是我们的假设,遗传基础反映MHC标记
英文摘要
It is our hypothesis that a genetic basis reflected by MHC markers
underlies pharmacologic response (both antipsychotic in the case of
classical neuroleptic drugs and hematologic in the case of Clozapine) in
patients with schizophrenia. Our application proposes a two arm study of
immunogenetic mechanisms and pharmacologic response in schizophrenia.
Specifically, we will examine the association between MHC markers, in
particular, HLA-A1 and neuroleptic treatment response in patients with
schizophrenia, since a decrease frequency of the HLA-A1 antigen was found
in schizophrenics who were refractory to neuroleptic treatment. In a
previous study, we reported an increase in HLA-A1 and a decrease in HLA-A2
in patients responsive to neuroleptic treatment. In other experiments, we
will determine the therapeutic and supratherapeutic neuroleptic doses using
lymphocytes from HLA-A1 positive versus negative patients to test the
preferential effect of neuroleptics using an "in vitro" T cell activation
model. The second arm of the proposal is based on an association that was
found between the HLA B38 DR4 DQw3 haplotype (DRB1*0402 and DQB1*0302
alleles) and vulnerability to develop Clozapine-induced agranulocytosis
among treatment refractory Jewish patients. In addition, among non-Jewish
agranulocytosis patients, an increase in HLA-DR2 , DQw1 antigens has been
found. We will confirm that the MHC susceptibility haplotype (B38, DR4,
DQw3) predisposes Jewish patients to develop agranulocytosis following
Clozapine treatment. Also, we will determine the specific alleles by
PCR-RFLP and PCR-SSO methods for DR4, Dqw3 and DR2, Dqw1 involved in
Clozapine-induced agranulocytosis susceptibility in order to provide a more
reliable screening test for neuroleptic resistant individuals undergoing
Clozapine treatment in order to minimize the risk of such complication.
It is likely that a common MHC class II allele is responsible for
agranulocytosis susceptibility between these two groups. However, the
possibility of a second gene, yet to be discovered, and in linkage
disequilibrium with MHC alleles and responsible for agranulocytosis
susceptibility can not be eliminated at this moment.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
HLA CLASS I ON NK CELL SUBSETS, REPERTOIRE AND FUNCTION
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批准号:6829681
-
项目类别:
-
资助金额:$36.36万
-
财政年份:2003
-
负责人:EDMOND J YUNIS
-
依托单位:
STUDIES OF NK AND T CELLS IN RELATION TO THE MAJOR HISTOCOMPATIBILITY COMPLEX
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批准号:6109676
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项目类别:
-
资助金额:$44.31万
-
财政年份:1999
-
负责人:EDMOND J YUNIS
-
依托单位:
STUDIES OF NK AND T CELLS IN RELATION TO THE MAJOR HISTOCOMPATIBILITY COMPLEX
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批准号:6272668
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项目类别:
-
资助金额:$42.95万
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财政年份:1998
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负责人:EDMOND J YUNIS
-
依托单位:
STUDIES OF NK AND T CELLS IN RELATION TO THE MAJOR HISTOCOMPATIBILITY COMPLEX
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批准号:6241774
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项目类别:
-
资助金额:$41.64万
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财政年份:1997
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负责人:EDMOND J YUNIS
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依托单位:
IMMUNOPHARMACOGENETICS OF SCHIZOPHRENIA
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批准号:2247377
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项目类别:
-
资助金额:$29.82万
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财政年份:1992
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负责人:EDMOND J YUNIS
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依托单位:
CELLULAR MECHANISMS OF DRUG REACTIONS IN SCHIZOPHRENIA
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批准号:2033823
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项目类别:
-
资助金额:$16.18万
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财政年份:1992
-
负责人:EDMOND J YUNIS
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依托单位:
CELLULAR MECHANISMS OF DRUG REACTIONS IN SCHIZOPHRENIA
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批准号:2635493
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项目类别:
-
资助金额:$16.67万
-
财政年份:1992
-
负责人:EDMOND J YUNIS
-
依托单位:
IMMUNOPHARMACOGENETICS OF SCHIZOPHRENIA
-
批准号:2247379
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项目类别:
-
资助金额:$26.1万
-
财政年份:1992
-
负责人:EDMOND J YUNIS
-
依托单位:
CELLULAR MECHANISMS OF DRUG REACTIONS IN SCHIZOPHRENIA
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批准号:2858020
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项目类别:
-
资助金额:$17.17万
-
财政年份:1992
-
负责人:EDMOND J YUNIS
-
依托单位:
IMMUNOLOGICAL ASPECTS OF AGING
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批准号:3114406
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项目类别:
-
资助金额:$13.98万
-
财政年份:1980
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负责人:EDMOND J YUNIS
-
依托单位:
IMMUNOLOGICAL ASPECTS OF AGING
-
批准号:3114405
-
项目类别:
-
资助金额:$14.62万
-
财政年份:1980
-
负责人:EDMOND J YUNIS
-
依托单位:
HUMAN TL (HTL) REGION IN THE HLA LINKAGE GROUP
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批准号:3126984
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项目类别:
-
资助金额:$8.42万
-
财政年份:1980
-
负责人:EDMOND J YUNIS
-
依托单位:
IMMUNOLOGICAL ASPECTS OF AGING
-
批准号:3114401
-
项目类别:
-
资助金额:$13.67万
-
财政年份:1980
-
负责人:EDMOND J YUNIS
-
依托单位:
IMMUNOLOGICAL ASPECTS OF AGING
-
批准号:3114410
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项目类别:
-
资助金额:$16.78万
-
财政年份:1980
-
负责人:EDMOND J YUNIS
-
依托单位:
HUMAN TL (HTL) REGION IN THE HLA LINKAGE GROUP
-
批准号:3126983
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项目类别:
-
资助金额:$10.82万
-
财政年份:1980
-
负责人:EDMOND J YUNIS
-
依托单位:
IMMUNOLOGICAL ASPECTS OF AGING
-
批准号:3114403
-
项目类别:
-
资助金额:$4.01万
-
财政年份:1980
-
负责人:EDMOND J YUNIS
-
依托单位:
IMMUNOLOGICAL ASPECTS OF AGING
-
批准号:3114402
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项目类别:
-
资助金额:$14.66万
-
财政年份:1980
-
负责人:EDMOND J YUNIS
-
依托单位:
IMMUNOLOGICAL ASPECTS OF AGING
-
批准号:3114408
-
项目类别:
-
资助金额:$16.97万
-
财政年份:1980
-
负责人:EDMOND J YUNIS
-
依托单位:
IMMUNOLOGICAL ASPECTS OF AGING
-
批准号:3114409
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项目类别:
-
资助金额:$16.14万
-
财政年份:1980
-
负责人:EDMOND J YUNIS
-
依托单位:
IMMUNOLOGICAL ASPECTS OF AGING
-
批准号:3114404
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项目类别:
-
资助金额:$12.57万
-
财政年份:1980
-
负责人:EDMOND J YUNIS
-
依托单位:
海外基金