Ryan Dos Santos Costa1, Camila Alexandrina Figueiredo2, Maurıcio Lima Barreto3, Neuza Maria Alcantara-Neves4, Laura Cunha Rodrigues5, Alvaro A Cruz6, Candelaria Vergara7, Nicholas Rafaels7, Cassandra Foster7, Joseph Potee7, Monica Campbell7, Rasika A Mathias7, Kathleen C Barnes8. 1. Division of Allergy and Clinical Immunology, Johns Hopkins University, Baltimore, Maryland; Health Science Institute, Federal University of Bahia, Salvador, Bahia, Brazil. 2. Health Science Institute, Federal University of Bahia, Salvador, Bahia, Brazil. Electronic address: cavfigueiredo@gmail.com. 3. Public Health Institute, Federal University of Bahia, Salvador, Bahia, Brazil; Research Center Gonçalo Moniz, Fundação Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil. 4. Health Science Institute, Federal University of Bahia, Salvador, Bahia, Brazil. 5. London School of Hygiene and Tropical Medicine, London, England. 6. Center of Excellence in Asthma, Federal University of Bahia, Salvador, Bahia, Brazil. 7. Division of Allergy and Clinical Immunology, Johns Hopkins University, Baltimore, Maryland. 8. Division of Allergy and Clinical Immunology, Johns Hopkins University, Baltimore, Maryland; Department of Medicine, University of Colorado Denver, Aurora, Colorado.
Abstract
BACKGROUND: Allergic 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. OBJECTIVE: To evaluate the effects of genetic variations in the TGF-β1 on allergy and helminths infections in children. METHODS: We 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. RESULTS: We 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). CONCLUSION: Individuals 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.
BACKGROUND: Allergic 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. OBJECTIVE: To evaluate the effects of genetic variations in the TGF-β1 on allergy and helminths infections in children. METHODS: We 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. RESULTS: We 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). CONCLUSION: Individuals 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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