Yunis J J, Lieberman J, Yunis E J
Division of Immunogenetics, Dana-Farber Cancer Institute, Boston, Massachusetts.
Drug Saf. 1992;7 Suppl 1:7-9. doi: 10.2165/00002018-199200071-00005.
In order to determine associations between the major histocompatibility complex (MHC) and the development of clozapine-induced agranulocytosis, HLA typing was performed in a group of 42 clozapine-treated patients, of whom 11 had developed this adverse reaction. Among the patients with agranulocytosis, 7 (63%) were of Ashkenazi Jewish background and 4 (37%) were non-Jewish. An association between the HLA-B38, -DR4, -DQw3 haplotype and clozapine-induced agranulocytosis was found in all Jewish cases (7/7; 100%); in contrast only 4 of 21 (19%) Jewish control (nonagranulocytic) patients carried this haplotype. Among non-Jewish patients the HLA-DR2, -DQw1 haplotype was present in 4 of 4 (100%) patients with clozapine-induced agranulocytosis and in only 3 of 10 (30%) ethnically matched control patients. Our results indicate that gene products within the MHC could be involved in clozapine-mediated haematological toxicity.
为了确定主要组织相容性复合体（MHC）与氯氮平所致粒细胞缺乏症发生之间的关联，对一组42例接受氯氮平治疗的患者进行了HLA分型，其中11例出现了这种不良反应。在粒细胞缺乏症患者中，7例（63%）为阿什肯纳兹犹太背景，4例（37%）为非犹太背景。在所有犹太病例（7/7；100%）中发现HLA - B38、- DR4、- DQw3单倍型与氯氮平所致粒细胞缺乏症之间存在关联；相比之下，21例犹太对照（非粒细胞缺乏症）患者中只有4例（19%）携带此单倍型。在非犹太患者中，HLA - DR2、- DQw1单倍型在4例（100%）氯氮平所致粒细胞缺乏症患者中出现，而在10例种族匹配的对照患者中只有3例（30%）出现。我们的结果表明，MHC内的基因产物可能参与氯氮平介导的血液学毒性。
