Clozapine therapy presents a risk of agranulocytosis, necessitating monitoring of white blood cell count. The detection of benign ethnic neutropenia (BEN), in which neutropenia can be present without an increased risk of infection, is particularly important in preventing unnecessary withdrawal of clozapine. BEN is strongly linked to the CC homozygote of the single nucleotide polymorphism rs2814778 in the atypical chemokine receptor-1 (ACKR1) gene.

We introduced voluntary genetic testing for BEN in one of our clozapine clinics, with the aim of assessing the prevalence of undiagnosed BEN in patients on clozapine.

We offered genetic testing for BEN to patients undergoing medium- and long-term clozapine treatment, and conducted a comparative analysis of neutrophil counts across three identified groups: those previously diagnosed with BEN, those with newly discovered BEN and those confirmed by genetic testing not to have BEN.

We conducted genetic testing for BEN on 108 patients. Of these, 16 were already registered as having BEN and had the CC homozygote. A further 26 patients (24% of the cohort) who were previously not diagnosed with BEN by standard haematological monitoring were found to have the CC homozygote on genetic testing. Unadjusted mean neutrophil counts were lowest for those with previously diagnosed BEN (2.5 × 109/L, 95% CI 2.2–2.8; P < 0.001 v. other groups), but those with newly discovered BEN had mean counts that were significantly lower (4.1 × 109/L, 95% CI 3.6–4.7) than those with TT and CT genotypes (5.1 × 109/L, 95% CI 4.7–5.4; P = 0.006).

Undiagnosed BEN was common in our naturalistic cohort. The integration of genetic testing into standard monitoring would enhance the management of clozapine therapy, potentially allowing for the safe reintroduction or continuation of clozapine in patients with hitherto unrecognised BEN. All current and prospective clozapine patients should be genetically tested for BEN.

氯氮平治疗存在粒细胞缺乏症的风险，需要监测白细胞计数。检测良性种族中性粒细胞减少症 （BEN），其中可能存在中性粒细胞减少症，但感染风险不增加，对于防止氯氮平不必要的停药尤为重要。BEN 与非典型趋化因子受体 1 （ACKR1） 基因中单核苷酸多态性 rs2814778 的 CC 纯合子密切相关。

我们在我们的一家氯氮平诊所引入了 BEN 的自愿基因检测，目的是评估氯氮平患者中未确诊 BEN 的患病率。

我们为接受中长期氯氮平治疗的患者提供 BEN 基因检测，并对三个已确定的组中的中性粒细胞计数进行了比较分析： 先前诊断为 BEN 的患者、新发现 BEN 的患者和通过基因检测确认没有 BEN 的患者。

我们对 108 例患者进行了 BEN 基因检测。其中，16 例已经注册为具有 BEN 并且具有 CC 纯合子。另有 26 名先前未通过标准血液学监测诊断为 BEN 的患者 （占队列的 24%） 在基因检测中发现具有 CC 纯合子。对于先前诊断为 BEN 的患者，未经调整的平均中性粒细胞计数最低 （2.5 × 109/L，95% CI 2.2-2.8;P < 0.001 v. 其他组），但新发现 BEN 的患者的平均计数显著低于 TT 和 CT 基因型患者 （5.1 ×× 109/L，95% CI 4.7-5.4;P = 0.006）。

未确诊的 BEN 在我们的自然主义队列中很常见。将基因检测纳入标准监测将加强氯氮平治疗的管理，可能允许在迄今为止未被识别的 BEN 患者中安全地重新引入或继续使用氯氮平。所有当前和潜在的氯氮平患者都应进行 BEN 基因检测。