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Gene Encoding Duffy Antigen/Receptor for Chemokines Is Associated with Asthma and IgE in Three Populations

¹ Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland; ² Institute for Immunological Research, University of Cartagena, Cartagena, Colombia; ³ National Genome Center at Howard University, Washington, DC; ⁴ Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland; ⁵ Servico de Imunologia, Hospital Universitario Professor Edgard Santos, and ⁶ ProAR–Faculdade de Medicina, Federal University of Bahia, Salvador, Bahia, Brazil; ⁷ Faculty of Medicine, University of the West Indies, Cave Hill Campus, Cave Hill, Barbados; ⁸ Department of Medicine, Northwestern University, Feinberg School of Medicine, Chicago, Illinois; ⁹ Charité, Department of Pediatric Pneumonology and Immunology, Berlin, Germany; and ¹⁰ Genometrics Section, Inherited Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, Maryland

Correspondence and requests for reprints should be addressed to Kathleen C. Barnes, Ph.D., Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Room 3A.62, Baltimore, MD 21224. E-mail: kbarnes{at}jhmi.edu

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.

Key Words: Duffy antigen/receptor for chemokines • continental population groups • lung diseases • hypersensitivity

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject The prevalence and severity of allergic airway diseases is especially high among individuals of African descent, even after adjusting for demographic and socioeconomic factors. Although it is unknown to what extent genetic susceptibility contributes to disparities in risk for atopic asthma, both linkage and association studies have shown evidence of genetic differences among ethnic and racial groups. What This Study Adds to the Field In this study we demonstrate that a genetic variant that determines the lack of expression of the Duffy antigen/receptor for chemokines in African ancestry populations can explain, at least in part, the observed disparities across ethnic groups.

 

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