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首页> 外文期刊>The journal of clinical psychiatry >Candidate gene analysis identifies a polymorphism in HLA-DQB1 associated with clozapine-induced agranulocytosis.
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Candidate gene analysis identifies a polymorphism in HLA-DQB1 associated with clozapine-induced agranulocytosis.

机译：候选基因分析鉴定出与氯氮平诱导的粒细胞缺乏症相关的HLA-DQB1多态性。

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OBJECTIVE: Clozapine is considered to be the most efficacious drug to treat schizophrenia, although it is underutilized, partially due to a side effect of agranulocytosis. This analysis of 74 candidate genes was designed to identify an association between sequence variants and clozapine-induced agranulocytosis (CIA). METHOD: Blood and medical history were collected for 33 CIA cases and 54 clozapine-treated controls enrolled between April 2002 and December 2003. Significant markers from 4 genes were then assessed in an independently collected case-control cohort (49 CIA cases, 78 controls). RESULTS: Sequence variants in 5 genes were found to be associated with CIA in the first cohort: HLA-DQB1, HLA-C, DRD1, NTSR1, and CSF2RB. Sequence variants in HLA-DQB1 were also found to be associated with CIA in the second cohort. After refinement analyses of sequence variants in HLA-DQB1, a single SNP (single nucleotide polymorphism), 6672G>C, was found to be associated with risk for CIA; the odds of CIA are 16.9 times greater in patients who carry this marker compared to those who do not. CONCLUSIONS: A sequence variant (6672G>C) in HLA-DQB1 is associated with increased risk for CIA. This marker identifies a subset of patients with an exceptionally high risk of CIA, 1,175% higher than the overall clozapine-treated population under the current blood-monitoring system. Assessing risk for CIA by testing for this and other genetic variants yet to be determined may be clinically useful when deciding whether to begin or continue treatment with clozapine.
机译：目的：氯氮平被认为是治疗精神分裂症的最有效药物，尽管未被充分利用，部分原因是粒细胞缺乏症的副作用。对74个候选基因的分析旨在确定序列变异与氯氮平诱导的粒细胞缺乏症（CIA）之间的关联。方法：收集2002年4月至2003年12月之间33例CIA病例和54例接受氯氮平治疗的对照的血液和病史。然后在独立收集的病例对照队列（49例CIA病例，78例对照）中评估了4个基因的重要标志物。 。结果：在第一个队列中发现了5个基因的序列变异体与CIA相关：HLA-DQB1，HLA-C，DRD1，NTSR1和CSF2RB。在第二批研究中，还发现HLA-DQB1中的序列变异与CIA有关。在对HLA-DQB1中的序列变异进行精细分析之后，发现一个单一的SNP（单核苷酸多态性）6672G> C与CIA的风险有关;携带这种标记物的患者与没有携带这种标记物的患者相比，CIA的几率要高16.9倍。结论：HLA-DQB1中的序列变异（6672G> C）与CIA风险增加相关。该标记物可识别出具有较高CIA风险的一部分患者，比当前血液监测系统中接受氯氮平治疗的总体人群高1,175％。在决定是否开始或继续使用氯氮平治疗时，通过测试尚待确定的这种和其他遗传变异来评估CIA的风险可能在临床上有用。

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