Dettling M, Sachse C, Müller-Oerlinghausen B, Roots I, Brockmöller J, Rolfs A, Cascorbi I
Department of Psychiatry, University Hospital Benjamin Franklin, Free University of Berlin, Germany.
Pharmacopsychiatry. 2000 Nov;33(6):218-20. doi: 10.1055/s-2000-8359.
The pathomechanisms of most drug-induced agranulocytoses are unclear; however, there are some studies pointing to genetic determinants. Some drug-induced agranulocytoses such as clozapine-induced agranulocytosis (CA) may be regarded as an idiosyncratic drug reaction because of its preclinical and clinical characteristics. To study some aspects of the genetic background of CA further, polymorphisms of specific metabolizing enzyme systems of clozapine were examined. Thirty-one schizophrenic patients with CA and 77 schizophrenic comparison subjects without this adverse effect underwent genotyping of a recently discovered G(-463)A polymorphism of myeloperoxidase (MPO) gene and cytochrome P4502D6. Neither the MPO mutation nor specific genotypes of cytochrome P4502D6 were associated with CA. Both were equally distributed among CA patients and controls. Thus, our data suggest lack of evidence of an association of CA and genetically variable activity of these specific drug metabolizing enzymes; however, this may be due to statistical reasons only. Thus, further studies with greater CA samples are necessary to draw final conclusions about these genetically based hypotheses.
大多数药物性粒细胞缺乏症的发病机制尚不清楚；然而，有一些研究指向遗传决定因素。一些药物性粒细胞缺乏症，如氯氮平引起的粒细胞缺乏症（CA），由于其临床前和临床特征，可能被视为一种特异质性药物反应。为了进一步研究CA遗传背景的某些方面，对氯氮平特定代谢酶系统的多态性进行了检测。31例患有CA的精神分裂症患者和77例无此不良反应的精神分裂症对照受试者接受了最近发现的髓过氧化物酶（MPO）基因G（-463）A多态性和细胞色素P4502D6的基因分型。MPO突变和细胞色素P4502D6的特定基因型均与CA无关。两者在CA患者和对照组中的分布相同。因此，我们的数据表明缺乏证据支持CA与这些特定药物代谢酶的遗传可变活性之间存在关联；然而，这可能仅出于统计学原因。因此，需要更大样本量的CA研究才能对这些基于遗传的假说得出最终结论。
