Dataset Information

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

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.

SUBMITTER: Costa RD

PROVIDER: S-EPMC7612854 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Publications

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

Costa Ryan Dos Santos RD Figueiredo Camila Alexandrina CA Barreto Maurıcio Lima ML Alcantara-Neves Neuza Maria NM Rodrigues Laura Cunha LC Cruz Alvaro A AA Vergara Candelaria C Rafaels Nicholas N Foster Cassandra C Potee Joseph J Campbell Monica M Mathias Rasika A RA Barnes Kathleen C KC

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology 20170309 4

<h4>Background</h4>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 airw ...[more]

PMID: 28284979

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Project description:Thymic stromal lymphopoietin (TSLP), an IL7-like cytokine produced by bronchial epithelial cells is upregulated in asthma and induces dendritic cell maturation supporting a Th2 response. Environmental pollutants, including tobacco smoke and diesel exhaust particles upregulate TSLP suggesting that TSLP may be an interface between environmental pollution and immune responses in asthma. Since asthma is prevalent in urban communities, variants in the TSLP gene may be important in asthma susceptibility in these populations.To determine whether genetic variants in TSLP are associated with asthma in an urban admixed population. METHODOLOGY AND MAIN RESULTS: Ten tag-SNPs in the TSLP gene were analyzed for association with asthma using 387 clinically diagnosed asthmatic cases and 212 healthy controls from an urban admixed population. One SNP (rs1898671) showed nominally significant association with asthma (odds ratio (OR)?=?1.50; 95% confidence interval (95% CI): 1.09-2.05, p?=?0.01) after adjusting for age, BMI, income, education and population stratification. Association results were consistent using two different approaches to adjust for population stratification. When stratified by smoking status, the same SNP showed a significantly increased risk associated with asthma in ex-smokers (OR?=?2.00, 95% CI: 1.04-3.83, p?=?0.04) but not significant in never-smokers (OR?=?1.34; 95% CI: 0.93-1.94, p?=?0.11). Haplotype-specific score test indicated that an elevated risk for asthma was associated with a specific haplotype of TSLP involving SNP rs1898671 (OR?=?1.58, 95% CI: 1.10-2.27, p?=?0.01). Association of this SNP with asthma was confirmed in an independent large population-based cohort consortium study (OR?=?1.15, 95% CI: 1.07-1.23, p?=?0.0003) and the results stratified by smoking status were also validated (ex-smokers: OR?=?1.21, 95% CI: 1.08-1.34, p?=?0.003; never-smokers: OR?=?1.06, 95% CI: 0.94-1.17, p?=?0.33).Genetic variants in TSLP may contribute to asthma susceptibility in admixed urban populations with a gene and environment interaction.

Dataset Information

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

Background

Objective

Methods

Results

Conclusion

Publications

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

Similar Datasets

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