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Background: Helminth infections are associated with protection against allergies. It is postulated that IL-10 production after helminth infection suppresses skin hypersensitivity and increases IgG₄ production, protecting against allergies., Objective: We aimed to determine whether IL10 polymorphisms are associated with helminth infection and the risk of wheeze and allergy., Methods: Twelve IL10 single nucleotide polymorphisms were genotyped in 1353 children aged 4 to 11 years living in a poor urban area in Salvador, Brazil. Wheezing status, Ascaris lumbricoides and Trichuris trichiura infection, IL-10 production by peripheral blood leukocytes stimulated with A lumbricoides extract, serum total IgE levels, specific IgE levels, skin prick test responses to common aeroallergens, and IgG4 and IgE anti-A lumbricoides antibody levels were measured in all children. Association tests were performed by using logistic or linear regression when appropriate, including sex, age, helminth infection, and principal components for ancestry informative markers as covariates by using PLINK., Results: Allele G of marker rs3024496 was associated with the decreased production of IL-10 by peripheral blood leukocytes in response to A lumbricoides stimulation. Allele C of marker rs3024498 was negatively associated with helminth infection or its markers. Marker rs3024492 was positively associated with the risk of atopic wheeze, total IgE levels, and skin prick test responses to cockroach., Conclusions: Our findings suggest that IL10 polymorphisms might play a role in the production of IL-10, helminth infection, and allergy. We hypothesize that polymorphisms related to protection against helminths, which would offer an evolutionary advantage to subjects in the past, might be associated with increased risk of allergic diseases., Competing Interests: of potential conflict of interest: M. L. Barreto has received grants from the Wellcome Trust and the National Research Council–Brazil and is employed by the Federal University of Bahia. P. J. Cooper has received grants from the Wellcome Trust and is employed by the Liverpool School of Tropical Medicine. A. A. Cruz serves on boards for Merck Sharp & Dohme and Roche; has consultant arrangements with Mantecorp; receives grants from GlaxoSmithKline; receives payment for lectures from Merck Sharp & Dohme; has received travel/accommodations/meeting expenses from Merck Sharp & Dohme and Novartis; and has conducted clinical trials for AstraZeneca, Novartis, TAKEDA, Eurofarma, GlaxoSmithKline, and Genentech. L. C. Pontes-de-Carvalho is employed by the Ministry of Health, Brazil. C. Vergara, C. Foster, M. Campbell, and R. A. Mathias are employed by Johns Hopkins University and have received grants from the National Institutes of Health. K. C. Barnes serves on boards for Genentech; has consultant arrangements with Sanofi-Aventis and Sirius Genomics; is employed by Johns Hopkins University; has received grants from the National Institutes of Health/National Heart, Lung, and Blood Institute; has received payment for lectures from the “Evolution and Diseases of Modern Environments” Symposium, the Cincinnati Children’s Hospital Medical Center Allergy Conference, the 50th Annual Swineford Allergy Conference, and the American Academy of Allergy, Asthma & Immunology; and receives royalties from Up-To-Date. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Objective: To determine whether polymorphisms of the IL10 and IL17 genes are associated with severe asthma control and bronchodilator reversibility in children and adolescents with severe asthma. Methods: This was a cross-sectional study, nested within a prospective cohort study of patients with severe asthma. Two outcomes were evaluated: asthma control and bronchodilator reversibility. We extracted DNA from peripheral blood and genotyped three single nucleotide polymorphisms: rs3819024 and rs2275913 in the IL17A gene; and rs3024498 in the IL10 gene. For the association analyses, we performed logistic regression in three genetic models (allelic, additive, and dominant). Results: The rs3024498 C allele in the IL10 gene was associated with failure to achieve asthma control despite regular treatment (p = 0.02). However, the G allele of the IL17A rs3819024 polymorphism was associated with failure to respond to stimulation with a β2 agonist. The rs2275913 polymorphism of the IL17A gene showed no relationship with asthma control or bronchodilator reversibility. Conclusions: In pediatric patients with severe asthma, the IL10 polymorphism appears to be associated with failure to achieve clinical control, whereas the IL17A polymorphism appears to be associated with a worse bronchodilator response. Knowledge of the involvement of these polymorphisms opens future directions for pharmacogenetic studies and for the implementation of individualized therapeutic management of severe asthma in pediatric patients. [ABSTRACT FROM AUTHOR]