as a dimer. The critical DARC binding residues are concentrated at the dimer interface and along a relatively flat surface spanning portions of two subdomains. A study in Brazil confirmed the protective effect of FY*A/FY*O against malaria. In contrast the genotype FY*B/FY*O was associated with a greater risk. Asthma Asthma is more common and tends to be more severe in those of African descent. There appears to be a correlation with both total IgE levels and asthma and mutations in the Duffy antigen. Hematopoiesis Duffy antigen plays a fundamental role on hematopoiesis. Indeed, nucleated red blood cells present in the bone marrow have high expression of DARC, which facilitates their direct contact with hematopoietic stem cells. The absence of erythroid DARC alters hematopoiesis including stem and progenitor cells, which ultimately gives rise to phenotypically distinct neutrophils. As a result, mature neutrophils of Duffy-negative individuals carry more molecular "weapons" against infectious pathogens. Therefore, alternative physiological patterns of hematopoiesis and bone marrow cell outputs depend on the expression of DARC in the erythroid lineage. Benign ethnic neutropenia A significant proportion (25–50%) of otherwise healthy African Americans are known to have a persistently lower white blood cell count than the normal range defined for individuals of European ancestry—a condition known as benign ethnic neutropenia. This condition is also found in Arab Jordanians, Black Bedouin, Beta Israel, Yemenite Jews and West Indians. This condition is associated with a reduced capacity to mobilize bone marrow neutrophil reserves in response to corticosteroids, despite normal cellularity and maturation of all cell lines in bone marrow aspirates. Strongly suggestive evidence has been found that links condition to a mutation in the Duffy gene. The distinctive neutrophils that are formed in the absence of DARC on erythroid lineage (see above - role of DARC on hematopoieisis) readily leave the blood stream, which explains the apparent lower numbers of neutrophils in the blood of Duffy-negative individuals. Cancer Interactions between the metastasis suppressor KAI1 on tumor cells and the cytokine receptor DARC on adjacent vascular cells suppresses tumor metastasis. In human breast cancer samples low expression of the DARC protein is significantly associated with estrogen receptor status, both lymph node and distant metastasis and poor survival. Endotoxin response The procoagulant response to lipopolysaccharide (bacterial endotoxin) is reduced in Duffy antigen negative Africans compared with Duffy positive Whites. This difference is likely to involve additional genes. HIV infection A connection has been