Gene encoding Duffy antigen/receptor for chemokines is associated with asthma and IgE in three populations

Abstract

Rationale: Asthma prevalence and severity are high among underserved minorities, including those of African descent. The Duffy antigen/receptor for chemokines is the receptor for Plasmodium vivax on erythrocytes and functions as a chemokine-clearing receptor. Unlike European populations, decreased expression of the receptor on erythrocytes is common among populations of African descent, and results from a functional T-46C polymorphism (rs2814778) in the promoter. This variant provides an evolutionary advantage in malaria-endemic regions, because Duffy antigen/receptor for chemokines-negative erythrocytes are more resistant to infection by P. vivax.

Objectives: To determine the role of the rs2814778 polymorphism in asthma and atopy as measured by total serum IgE levels among four populations of African descent (African Caribbean, African American, Brazilian, and Colombian) and a European American population.

Methods: Family-based association tests were performed in each of the five populations to test for association between the rs2814778 polymorphism and asthma or total IgE concentration.

Measurements and main results: Asthma was significantly associated with the rs2814778 polymorphism in the African Caribbean, Colombian, and Brazilian families (P < 0.05). High total IgE levels were associated with this variant in African Caribbean and Colombian families (P < 0.05). The variant allele was not polymorphic among European Americans.

Conclusions: Susceptibility to asthma and atopy among certain populations of African descent is influenced by a functional polymorphism in the gene encoding Duffy antigen/receptor for chemokines. This genetic variant, which confers resistance to malarial parasitic infection, may also partially explain ethnic differences in morbidity of asthma.

Figure 1.

Gene encoding Duffy antigen/receptor for chemokines (DARC) T-46C allele and genotype frequencies among African Caribbean, African American, Brazilian, Colombian, and European American founders.

Figure 2.

Comparison of total IgE levels between carriers of the CC genotype and carriers of the combined CC and CT genotypes among unrelated subjects with asthma within (A) African Caribbean, (B) African American, (C) Colombian, and (D) Brazilian groups. No comparisons were performed among the European Americans because of the low frequency of the CC genotype (0.4%) in this population. The line in the middle of the box represents the median and the lines that form the box correspond to the 25th and 75th percentiles.