Many medical treatments, from oncology to psychiatry, can lower white blood cell counts and thus access to these treatments can be restricted to individuals with normal levels of white blood cells, principally in order to minimize risk of serious infection. This adversely affects individuals of African or Middle Eastern ancestries who have on average a reduced number of circulating white blood cells, because of the Duffy-null (CC) genotype at rs2814778 in the ACKR1 gene. Here, we investigate whether the Duffy-null genotype is associated with the risk of infection using the UK Biobank sample and the iPSYCH Danish case-cohort study, two population-based samples from different countries and age ranges. We found that a high proportion of those with the Duffy-null genotype (21%) had a neutrophil count below the threshold often used as a cut-off for access to relevant treatments, compared with 1% of those with the TC/TT genotype. In addition we found that despite its strong association with lower average neutrophil counts, the Duffy-null genotype was not associated with an increased risk of infection, viral or bacterial. These results have widespread implications for the clinical treatment of individuals of African ancestry and indicate that neutrophil thresholds to access treatments could be lowered in individuals with the Duffy-null genotype without an increased risk of infection.

中文翻译：

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达菲无效基因型和感染风险。


从肿瘤学到精神病学的许多医学治疗都可以降低白细胞计数，因此只有白细胞水平正常的个体才能获得这些治疗，主要是为了最大限度地降低严重感染的风险。这对非洲或中东血统的个体产生不利影响，由于ACKR1基因中 rs2814778 处的达菲无效 (CC) 基因型，这些人的循环白细胞数量平均减少。在这里，我们使用英国生物银行样本和 iPSYCH 丹麦病例队列研究（来自不同国家和年龄范围的两个基于人群的样本）调查 Duffy 无效基因型是否与感染风险相关。我们发现，大部分 Duffy 无效基因型患者 (21%) 的中性粒细胞计数低于通常用作获得相关治疗的临界值的阈值，而 TC/TT 基因型患者中只有 1% 的中性粒细胞计数低于该阈值。 。此外，我们发现，尽管达菲缺失基因型与较低的平均中性粒细胞计数密切相关，但它与病毒或细菌感染风险增加无关。这些结果对非洲血统个体的临床治疗具有广泛的影响，并表明具有达菲缺失基因型的个体接受治疗的中性粒细胞阈值可以降低，而不会增加感染风险。