What is the cause of constitutional/ethnic neutropenia?

By William Aird

Homozygosity of the single nucleotide polymorphism (SNP) rs2814778 located in the promoter region of the Duffy Antigen Receptor for Chemokines (DARC) also named Atypical chemokine receptor 1 (ACKR1) gene. This variant codes the Duffy negative [Fy(a-b-)] blood group. The Duffy positive phenotype is found in only 0.2% of Africans and 99.3% of Europeans. Duffy null polymorphism associated with protection against invasion of red blood cells by Plasmodium vivax malaria. Mechanism of lack of DARC and associated neutropenia unknown.

According to Donadieu et al:

Although this clinically insignificant variant most often seen in those of African descent has historically been called ‘benign ethnic neutropenia,’ we feel this name is problematic as it implies that ethnicity is causative and that this is a disease that requires intervention. We advocate for an alternative name such as chronic benign neutropenia, Duffy null associated neutrophil count, or typical neutrophil count with Fy (a-b-) status that reflects the genetic underpinning of this variant and highlights that it is not a disease state. Consensus has yet to be reached for an alternative name or expected ranges of normal neutrophil counts.