Reassurance for Patients with Duffy-Null Associated Neutrophil Counts

A variant in the atypical chemokine receptor 1 (ACKR1) gene (rs2814778) associates with loss of the Duffy A and B antigens on red blood cell surfaces and lower white blood cell counts. This variant confers resistance to Plasmodium vivax malaria, accounting for high prevalence among persons with ancestry from malaria-endemic regions. Hematologists now classify a reduced leukocyte/neutrophil count in this setting as a “Duffy-null associated neutrophil count.” Referrals are still common given concern for primary marrow disorders or infectious complications. Further, patients with cancer and this variant can be excluded from clinical trials or receive unnecessary modifications to their chemotherapy regimens due to concerns presented by a lower white cell count. These investigators conducted a phenome-wide association study to identify any links between the rs2814778 variant and >1400 clinical conditions among a population-based cohort (the All of Us Research Program).

Although individuals with Duffy-null status had lower white cell and neutrophil counts than those with other genotypes, Duffy-null status was not associated with any of the clinical conditions (including sepsis, pneumonia, abscesses, or diarrhea). A unique finding was an association with the Duffy-null variant and Middle Eastern (14%), Pacific Islander (7%), and Hispanic ancestry (5%).