TY - JOUR
T1 - Coassociations between IL10 polymorphisms, IL-10 production, helminth infection, and asthma/wheeze in an urban tropical population in Brazil
AU - Figueiredo, Camila Alexandrina
AU - Barreto, Maurício Lima
AU - Alcantara-Neves, Neuza Maria
AU - Rodrigues, Laura Cunha
AU - Cooper, Philip John
AU - Cruz, Alvaro A.
AU - Pontes-De-Carvalho, Lain Carlos
AU - Lemaire, Denise C.
AU - Dos Santos Costa, Ryan
AU - Amorim, Leila D.
AU - Vergara, Candelaria
AU - Rafaels, Nicholas
AU - Gao, Li
AU - Foster, Cassandra
AU - Campbell, Monica
AU - Mathias, Rasika A.
AU - Barnes, Kathleen C.
N1 - Funding Information:
Supported by the Wellcome Trust, UK ; the HCPC Latin America Excellence Centre Programme , Ref 072405/Z/03/Z ; the Brazilian agency Conselho Nacional de Desenvolvimento Científico e Tecnológico–CNPq ; and the David G. Marsh Award . K.C.B. was supported in part by the Mary Beryl Patch Turnbull Scholar Program .
Funding Information:
Disclosure 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.
PY - 2013/6
Y1 - 2013/6
N2 - 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.
AB - 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.
KW - IL10
KW - Social Changes Asthma and Allergy in Latin America
KW - allergy
KW - asthma
KW - helminth infection
KW - immune modulation
KW - polymorphisms
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U2 - 10.1016/j.jaci.2012.10.043
DO - 10.1016/j.jaci.2012.10.043
M3 - Article
C2 - 23273955
AN - SCOPUS:84878535546
SN - 0091-6749
VL - 131
SP - 1683
EP - 1690
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 6
ER -