Distinct transcript isoforms of the atypical chemokine receptor 1 (ACKR1) / Duffy Antigen Receptor for Chemokines (DARC) gene are expressed in lymphoblasts and altered isoform levels are associated with genetic ancestry and the duffy-null allele

Melissa B Davis, Andrea Walens, Rupali Hire, Kauthar Mumin, Andrea M. Brown, De Juana Ford, Elizabeth W. Howerth, Michele Anne Monteil

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The Atypical ChemoKine Receptor 1 (ACKR1) gene, better known as Duffy Antigen Receptor for Chemokines (DARC or Duffy), is responsible for the Duffy Blood Group and plays a major role in regulating the circulating homeostatic levels of pro-inflammatory chemokines. Previous studies have shown that one common variant, the Duffy Null (Fy-) allele that is specific to African Ancestry groups, completely removes expression of the gene on erythrocytes; however, these individuals retain endothelial expression. Additional alleles are associated with a myriad of clinical outcomes related to immune responses and inflammation. In addition to allele variants, there are two distinct transcript isoforms of DARC which are expressed from separate promoters, and very little is known about the distinct transcriptional regulation or the distinct functionality of these protein isoforms. Our objective was to determine if the African specific Fy- allele alters the expression pattern of DARC isoforms and therefore could potentially result in a unique signature of the gene products, commonly referred to as antigens. Our work is the first to establish that there is expression of DARC on lymphoblasts. Our data indicates that people of African ancestry have distinct relative levels of DARC isoforms expressed in these cells. We conclude that the expression of both isoforms in combination with alternate alleles yields multiple Duffy antigens in ancestry groups, depending upon the haplotypes across the gene. Importantly, we hypothesize that DARC isoform expression patterns will translate into ancestry-specific inflammatory responses that are correlated with the axis of pro-inflammatory chemokine levels and distinct isoformspecific interactions with these chemokines. Ultimately, this work will increase knowledge of biological mechanisms underlying disparate clinical outcomes of inflammatory-related diseases among ethnic and geographic ancestry groups.

Original languageEnglish (US)
Article number140098
JournalPLoS One
Volume10
Issue number10
DOIs
StatePublished - Oct 16 2015

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Antigen Receptors
null alleles
Chemokine Receptors
Chemokines
Protein Isoforms
ancestry
Genes
Alleles
antigens
genes
chemokines
alleles
inflammation
chemokine receptors
protein isoforms
Antigens
blood groups
Blood Group Antigens
Haplotypes
haplotypes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Distinct transcript isoforms of the atypical chemokine receptor 1 (ACKR1) / Duffy Antigen Receptor for Chemokines (DARC) gene are expressed in lymphoblasts and altered isoform levels are associated with genetic ancestry and the duffy-null allele. / Davis, Melissa B; Walens, Andrea; Hire, Rupali; Mumin, Kauthar; Brown, Andrea M.; Ford, De Juana; Howerth, Elizabeth W.; Monteil, Michele Anne.

In: PLoS One, Vol. 10, No. 10, 140098, 16.10.2015.

Research output: Contribution to journalArticle

Davis, Melissa B ; Walens, Andrea ; Hire, Rupali ; Mumin, Kauthar ; Brown, Andrea M. ; Ford, De Juana ; Howerth, Elizabeth W. ; Monteil, Michele Anne. / Distinct transcript isoforms of the atypical chemokine receptor 1 (ACKR1) / Duffy Antigen Receptor for Chemokines (DARC) gene are expressed in lymphoblasts and altered isoform levels are associated with genetic ancestry and the duffy-null allele. In: PLoS One. 2015 ; Vol. 10, No. 10.
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