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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. [ABSTRACT FROM AUTHOR]

BACKGROUND: Evidence of genetic control for total serum IgE (tIgE) level has been reported in multiple populations, although populations with substantial exposure to helminths have yielded lower estimates of heritability, despite evidence suggesting that genes also control a significant portion of the variation in the number of Schistosoma mansoni eggs per gram of fecal matter. METHODS: By use of a whole-population ascertainment scheme, 822 individuals were enrolled from a schistosomiasis-endemic area in Conde, Bahia, in Brazil. Heritability was estimated by using an additive polygenic model, and segregation analysis was performed for 2 quantitative traits, tIgE level and egg count. RESULTS: After adjusting for nongenetic covariates, the heritability of log-transformed tIgE level and log-transformed egg count was estimated at 60% and 31%, respectively. No evidence for a single major gene controlling tIgE level or egg count was observed in segregation analysis for 781 individuals and 403 individuals, respectively, in 318 families, however, which suggests complex biological control. CONCLUSIONS: The high heritability of tIgE level indicates that genetic factors are likely to control tIgE level even in the presence of helminthic infection. Substantial heritability for the burden of S. mansoni infection was confirmed in these Brazilian families. Further genetic studies will be needed to dissect the specific genetic factors that underlie these traits. Copyright © 2008 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

OBJECTIVE: Protein citrullination is an important posttranslational modification recognized by rheumatoid arthritis (RA)-specific autoantibodies. One of the citrullinating enzymes, peptidyl arginine deiminase type 4 (PAD-4), is genetically associated with development of RA in some populations, although the mechanism(s) mediating this effect are not yet clear. There have been descriptions of anti-PAD-4 autoantibodies in different rheumatic diseases. This study was undertaken to investigate whether anti-PAD-4 antibodies are specific to RA, are associated with disease phenotype or severity, and whether PAD-4 polymorphisms influence the anti-PAD-4 autoantibody response. METHODS: Sera from patients with established RA, patients with other rheumatic diseases, and healthy adults were assayed for anti-PAD-4 autoantibodies by immunoprecipitation of in vitro-translated PAD-4. The epitope(s) recognized by PAD-4 autoantibodies were mapped using various PAD-4 truncations. PAD-4 genotyping was performed on RA patients with the TaqMan assay. Joint erosions were scored from hand and foot radiographs using the Sharp/van der Heijde method. RESULTS: PAD-4 autoantibodies were found in 36-42% of RA patients, and were very infrequent in controls. Recognition by anti-PAD-4 autoantibodies required the 119 N-terminal amino acids, which encompass the 3 nonsynonymous polymorphisms associated with disease susceptibility. Strikingly, the anti-PAD-4 immune response was associated with the RA susceptibility haplotype of PADI4. Anti-PAD-4 antibodies were associated with more severe joint destruction in RA. CONCLUSION: Our findings indicate that anti-PAD-4 antibodies are specific markers of RA, independently associated with more severe disease, suggesting that an anti-PAD-4 immune response may be involved in pathways of joint damage in this disease. Polymorphisms in the PADI4 gene influence the immune response to the PAD-4 protein, potentially contributing to disease propagation. [ABSTRACT FROM AUTHOR]