Maria L. Stockton

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

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.

A novel promoter polymorphism in the gene encoding complement component 5 receptor 1 on chromosome 19q13.3 is not associated with asthma and atopy in three independent populations

Background The inflammatory functions of complement component 5 (C5) are mediated by its receptor, C5R1, which is expressed on bronchial, epithelial, vascular endothelial and smooth muscle cells. A susceptibility locus for murine allergen‐induced airway hyper‐responsiveness was identified in a region syntenic to human chromosome 19q13, where linkage to asthma has been demonstrated and where the gene encoding C5R1 is localized.

Inheritance of Total Serum IgE in the Isolated Tangier Island Population from Virginia: Complexities Associated with Genealogical Depth of Pedigrees in Segregation Analyses

Objectives: This study was aimed at performing a segregation analysis of total serum immunoglobulin E (tIgE) in an isolated population using maximal genealogical information permitted by current software and computer capacities, while assessing the reliability of the best-fitting model of inheritance for tIgE through simulations. Methods: All current Tangier Island, VA, residents (n = 664) belonged to one large extended pedigree (n = 3,501) spanning 13 generations, with an average inbreeding coefficient of 0.009. Phenotype data were obtained on 453 (68.2%) of the residents using a population-based recruitment scheme. Due to computational limitations resulting from the extremely complex pedigree structure, analysis on only two pedigree reconstructions was feasible: a reduced pedigree retaining all phenotyped individuals and their parents as 57 distinct families, and 922 nuclear families. Results: Familial correlations and heritability calculations reveal a significant genetic component to tIgE in these data (heritability = 26%). The most parsimonious model to explain tIgE distribution indicated by the reduced pedigree structure was a two-distribution Mendelian model. However, larger and non-genetic models could not be rejected. Simulations over 200 replicates performed to evaluate the reliability of this model, indicated that using restricted genealogical information had minimal impact on results of segregation anal yses performed here.