Tumor Necrosis Factor Constellation Polymorphism and Clozapine-Induced Agranulocytosis in Two Different Ethnic Groups
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- David Turbay
- From the Department of Pathology, Harvard Medical School and Division of Immunogenetics, Dana-Farber Cancer Institute, Boston, MA; the Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill; and the Center for Blood Research, Boston, MA.
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- Jeffrey Lieberman
- From the Department of Pathology, Harvard Medical School and Division of Immunogenetics, Dana-Farber Cancer Institute, Boston, MA; the Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill; and the Center for Blood Research, Boston, MA.
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- Chester A. Alper
- From the Department of Pathology, Harvard Medical School and Division of Immunogenetics, Dana-Farber Cancer Institute, Boston, MA; the Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill; and the Center for Blood Research, Boston, MA.
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- Julio C. Delgado
- From the Department of Pathology, Harvard Medical School and Division of Immunogenetics, Dana-Farber Cancer Institute, Boston, MA; the Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill; and the Center for Blood Research, Boston, MA.
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- Deyanira Corzo
- From the Department of Pathology, Harvard Medical School and Division of Immunogenetics, Dana-Farber Cancer Institute, Boston, MA; the Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill; and the Center for Blood Research, Boston, MA.
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- Juan J. Yunis
- From the Department of Pathology, Harvard Medical School and Division of Immunogenetics, Dana-Farber Cancer Institute, Boston, MA; the Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill; and the Center for Blood Research, Boston, MA.
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- Edmond J. Yunis
- From the Department of Pathology, Harvard Medical School and Division of Immunogenetics, Dana-Farber Cancer Institute, Boston, MA; the Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill; and the Center for Blood Research, Boston, MA.
書誌事項
- 公開日
- 1997-06-01
- DOI
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- 10.1182/blood.v89.11.4167
- 公開者
- American Society of Hematology
この論文をさがす
説明
<jats:title>Abstract</jats:title><jats:p>Genes of the major histocompatibility complex (MHC) are associated with susceptibility to different immune and nonimmune mediated diseases. We had reported that the drug adverse reaction, clozapine-induced agranulocytosis (CA), is associated with different HLA types and HSP70 variants in Ashkenazi Jewish and non-Jewish patients, suggesting that a gene within the MHC region is associated with CA. This study was designed to find common genetic markers for this disorder in both ethnic groups. The tumor necrosis factor (TNF ) microsatellites d3 and b4 were found in higher frequencies in both Jewish and nonJewish patients: 51 of 66 (77%) and 48 of 66 (57%), respectively. Comparisons of these frequencies with those of controls, 28 of 66 (42%) and 18 of 66 (27%), were statistically significant (corrected P value = .001 for the d3 allele and .0005 for the b4 allele). On the other hand, the TNF microsatellite b5 was underrepresented in the group of patients, 9 of 66 (14%), when compared with the control subjects, 43 of 66 (65%) (corrected P value = .0005), probably related to protection from CA. Our results show a strong association of some genetic variants of the TNF loci with susceptibility to CA in two different ethnic groups suggesting involvement of TNF and/or associated gene(s) products in the pathogenesis of this hematologic-drug adverse reaction.</jats:p>
収録刊行物
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- Blood
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Blood 89 (11), 4167-4174, 1997-06-01
American Society of Hematology