4.7 Article

Coassociations between IL10 polymorphisms, IL-10 production, helminth infection, and asthma/wheeze in an urban tropical population in Brazil

Journal

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 131, Issue 6, Pages 1683-1690

Publisher

MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2012.10.043

Keywords

IL10; polymorphisms; helminth infection; immune modulation; allergy; asthma; Social Changes Asthma and Allergy in Latin America

Funding

  1. Wellcome Trust, UK
  2. HCPC Latin America Excellence Centre Programme [072405/Z/03/Z]
  3. Brazilian agency Conselho Nacional de Desenvolvimento Cientifico e Tecnologico-CNPq
  4. David G. Marsh Award
  5. Mary Beryl Patch Turnbull Scholar Program
  6. Wellcome Trust
  7. National Research Council-Brazil
  8. GlaxoSmithKline
  9. Merck Sharp Dohme
  10. Novartis
  11. National Institutes of Health
  12. National Institutes of Health/National Heart, Lung, and Blood Institute
  13. Evolution and Diseases of Modern Environments Symposium
  14. Cincinnati Children's Hospital Medical Center Allergy Conference

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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 IgG(4) 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 IgG(4) 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.

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