Effect of polymorphisms on TGFB1 on allergic asthma and helminth infection in an African admixed population

Publication date: Available online 9 March 2017
Source:Annals of Allergy, Asthma & Immunology
Author(s): Ryan dos Santos Costa, Camila Alexandrina Figueiredo, Maurıcio Lima Barreto, Neuza Maria Alcantara-Neves, Laura Cunha Rodrigues, Alvaro A. Cruz, Candelaria Vergara, Nicholas Rafaels, Cassandra Foster, Joseph Potee, Monica Campbell, Rasika A. Mathias, Kathleen C. Barnes
BackgroundAllergic asthma is a complex disorder that results from a combination of genetic and environmental factors. Studies suggest that helminth infections can activate a regulatory network characterized by the production of regulatory cytokines, such as interleukin 10 and transforming growth factor β1 (TGF-β1) and subsequently protect against immune-mediated diseases, such as asthma. On the other hand, TGF-β1 is increased in the lungs of individuals with asthma and may modulate airway inflammation. The role of TGF- β 1 single-nucleotide polymorphisms (SNPs) in allergic disease remains inconclusive.ObjectiveTo evaluate the effects of genetic variations in the TGF-β1 on allergy and helminths infections in children.MethodsWe tested for association among 4 TGF-β1 SNPs and allergic asthma, specific IgE, skin prick test result, and IL-10 production in 1,335 Brazilians. In addition, we analyzed the association with markers of helminth infection (parasite burden, anti-Ascaris IgE, and worm specific IgG4). The polymorphisms were genotyped using Taq Man probes.ResultsWe found an association between rs1800470 (C allele) and atopic wheezing (odds ratio [OR], 0.60; 95% confidence interval [CI], 0.37–0.95) and markers of allergy (OR, 0.41; 95% CI, 0.22–0.79). In contrast, a positive association was observed between the haplotype ACCA and Trichuris trichiura infection (OR, 1.85; P = .003) and Ascaris lumbricoides infection (OR, 2.01; P < .001). This haplotype was also associated with increased IL-10 production (β = 50.7; P < .001).ConclusionIndividuals with TGF-β1 polymorphisms have an increased susceptibility to helminth infections and a lower risk of developing allergy. These studies suggest that immune modulation of allergic disease results not only from environmental factors but also from genetic susceptibility and IL-10 production.



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