Duffy (Fy), DARC, and neutropenia among women from the United States, Europe and the Caribbean

Abstract

Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation. SummaryNeutropenia associated with race/ethnicity has essentially been unexplained and, although thought to be benign, may affect therapy for cancer or other illnesses. A recent study linked a single nucleotide polymorphism (SNP) (rs2814778) in the Duffy antigen/receptor chemokine gene (DARC) with white blood cell count. We therefore analysed the association of the rs2814778 CC, TC and TT genotypes with absolute neutrophil count (ANC) among asymptomatic women from the Caribbean, Europe and the United States. Among 261 study participants, 33/47 women from Barbados/ Trinidad-Tobago, 34/49 from Haiti, 26/37 from Jamaica, and 29/38 USborn black women, but only 4/50 from the Dominican Republic and 0/40 US-or European-born whites (P = 0AE0001) had the CC genotype. In a linear regression model that included percentage African ancestry, national origin, cytokines, socio-economic factors and the ELA2 rs57834246 SNP, only the DARC rs2814778 genotype and C-reactive protein were associated with ANC (P < 0AE0001). Women with the CC genotype had lower ANC than other women. Further research is needed on the associations of rs2814778 genotype with neutropenia and treatment delay in the setting of cancer. A better understanding of these associations may help to improve cancer outcomes among individuals of African ancestry.

The Duffy-null state is associated with a survival advantage in leukopenic HIV-infected persons of African ancestry

“…The levels of total lymphocytes or CD4 ϩ and CD8 ϩ T cells were similar among AAs with different DARC genotypes. Hence, concordant with published reports, [21][22][23][24] the lower WBC levels found in Ϫ46C/C-bearing HIV ϩ AAs we suspect are because of a reduction in neutrophil and, possibly, monocyte cell counts.…”

“…First, admixture mapping and other genetic studies in large nonimmunosuppressed cohorts of EAs and AAs demonstrate that, over and above its strong link with African ancestry, DARC Ϫ46C/C is the main genetic basis for ethnic leukopenia 21 and neutropenia 22 ; other observational studies substantiate this relationship between DARC Ϫ46C/C genotype and leukopenia or neutropenia. 23,24 Second, in our study population of HIV ϩ AAs, those with the DARC Ϫ46C/C genotype had a slower rate of HIV disease progression than those with DARC ϪT/T or C/T. 10 The latter 2 findings provided the rationale for investigating further the relationships among leukopenia, DARC genotype, and HIV disease course.…”

Clinical Characteristics of Severe Congenital Neutropenia Caused by Novel ELANE Gene Mutations

“…5 Neutropenia in some black populations is associated with a particular polymorphism in the gene encoding Duffy antigen receptor for cytokines. 20 Here, we examined only the ELANE and WAS genes (no other gene that may caused SCN) and thus we cannot yet conclude whether SCN in the Chinese population is caused more frequently by mutations in ELANE than by mutations in other genes.…”

Race-related health disparities and biological aging: Does rate of telomere shortening differ across blacks and whites?

“…Repeated measures over time and at other life stages would provide more detailed information and insight into when disparities in LTLs begin to be evident. Prior work has suggested some differences in total cell counts or proportion of cells by race/ethnicity (Bain, 1996; Freedman et al, 1997; Grann et al, 2008; Lim et al, 2010). Information about leukocyte fractionation is not available for our samples, thus we were unable to directly assess whether this might account for some of our findings.…”