More than 25 years of genetic studies of clozapine-induced agranulocytosis

被引：30

作者：

de With, S. A. J. ^{[1
]}

Pulit, S. L. ^{[2
]}

Staal, W. G. ^{[3
,4
,5
]}

Kahn, R. S. ^{[1
]}

Ophoff, R. A. ^{[1
,6
]}

机构：

[1] Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Psychiat, Utrecht, Netherlands

[2] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands

[3] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Cognit Neurosci, Nijmegen, Netherlands

[4] Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, Nijmegen, Netherlands

[5] Karakter, Ctr Child & Adolescent Psychiat, Nijmegen, Netherlands

[6] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, UCLA Ctr Neurobehav Genet, Los Angeles, CA 90024 USA

来源：

PHARMACOGENOMICS JOURNAL | 2017年 / 17卷 / 04期

关键词：

DRUG-INDUCED AGRANULOCYTOSIS; TOXIC EPIDERMAL NECROLYSIS; STEVENS-JOHNSON-SYNDROME; GENOME-WIDE ASSOCIATION; DIFFERENT ETHNIC-GROUPS; RHEUMATOID-ARTHRITIS; MONOZYGOTIC TWINS; SCHIZOPHRENIA; RISK; POLYMORPHISMS;

D O I：

10.1038/tpj.2017.6

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Clozapine is one of the most effective atypical antipsychotic drugs prescribed to patients with treatment-resistant schizophrenia. Approximately 1% of patients experience potential life-threatening adverse effects in the form of agranulocytosis, greatly hindering its applicability in clinical practice. The etiology of clozapine-induced agranulocytosis (CIA) remains unclear, but is thought to be a heritable trait. We reviewed the genetic studies of CIA published thus far. One recurrent finding from early candidate gene study to more recent genome-wide analysis is that of the involvement of human leukocyte antigen locus. We conclude that CIA is most likely a complex, polygenic trait, which may hamper efforts to the development of a genetic predictor test with clinical relevance. To decipher the genetic architecture of CIA, it is necessary to apply more rigorous standards of phenotyping and study much larger sample sizes.

引用

页码：304 / 311

页数：8

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