Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/25536
Title: IL33 and IL1RL1 variants are associated with asthma and atopy in a Brazilian population
Authors: Queiroz, Gerson de Almeida
Costa, Ryan dos Santos
Neves, Neuza Maria Alcântara
Costa, Gustavo Nunes de Oliveira
Barreto, Mauricio Lima
Carneiro, Valdirene Leão
Figueiredo, Camila Alexandrina Viana de
Affilliation: Federal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, Brazil
Federal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, Brazil
Federal University of Bahia. Laboratory of Allergy and Acarology. Salvador, BA, Brazil
Federal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Federal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, Brazil
Federal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, Brazil
Abstract: Atopic asthma is a chronic inflammatory disease in airways resulting from genetic and environmental factors, characterized by production of the Th2 cytokines interleukin-4 (IL-4), interleukin-5 (IL-5) and interleukin-13 (IL-13). Interleukin-33 (IL-33) appears to be a potent inducer of Th2 immune response. This occurs when IL-33 binds and activates its receptor, the membrane ST2 (ST2L) in mast cells, dendritic cells, basophils, eosinophils, innate lymphoids and Th2 cells, leading to the release of these cytokines and intensifying allergic inflammation. Polymorphisms in the IL33 and IL1RL1 can act as protective or risk factors for asthma and/or allergy in humans. No study was conducted to replicate such findings in a European and African descendent mixed population. DNA was extracted from peripheral blood from 1223 subjects, and the samples were genotyped using Illumina 2.5 Human Omni Beadchip. We tested for possible associations between SNPs in the IL33 and ST2 with asthma and allergy markers such as specific IgE (sIgE), IL-5 and IL-13 production and skin prick test (SPT). Logistics regressions were performed using PLINK software 1.07. The analyses were adjusted for sex, age, helminth infection and ancestry markers. The G allele of IL33 SNP rs12551256 was negatively associated with asthma (OR 0.71, 95% CI: 0.53-0.94, P = 0.017). In contrast, the A allele of IL1RL1 rs1041973 was positively associated with IL-5 production (OR 1.36, 95% CI: 1.09-1.84, P = 0.044), sIgE levels (OR 1.40, 95% CI: 1.07-1.84, P = 0.013) and positive SPT (OR 1.48, 95% CI: 1.08-2.03, P = 0.014), for Blomia tropicalis mite. The same allele, in atopic subjects, was associated with decreased production of soluble ST2 (sST2) (P < 0.05). Moreover, expression quantitative trait loci (eQTL) analysis suggests that rs1041973 and rs873022 regulate the expression of IL1RL1 gene. This latest SNP, rs873022, the T allele, was also associated with a lower production of sST2 in plasma of Brazilians. The genetic risk score for rs1041973 and rs16924161 demonstrated a higher risk for SPT positivity against B. tropicalis, the greater the number of risk alleles for both SNPs. Our findings demonstrate a robust association of genetic variants in IL1RL1 and IL33 SNPs with allergy markers and asthma.
Keywords: Asthma
Skin
Mites
Polymorphism, Single Nucleotide
Genetic Predisposition to Disease
Humans
keywords: Asma
Pele
Ácaros
Polimorfismo de Nucleotídeo Único
Predisposição Genética para Doença
Humanos
Issue Date: 2017
Publisher: Wiley
Citation: QUEIROZ, G. A. et al. IL33 and IL1RL1 variants are associated with asthma and atopy in a Brazilian population. International Journal of Immunogenetics, v. 44, p. 51–61, 2017.
DOI: 10.1111/iji.12306
ISSN: 1744-3121
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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