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

Ann Allergy Asthma Immunol. 2017 Apr;118(4):483-488.e1. doi: 10.1016/j.anai.2017.01.028. Epub 2017 Mar 9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Asthma / epidemiology
  • Asthma / etiology*
  • Brazil / epidemiology
  • Brazil / ethnology
  • Child
  • Child, Preschool
  • Ethnic Groups*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genotype
  • Haplotypes
  • Helminthiasis / epidemiology
  • Helminthiasis / etiology*
  • Humans
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology
  • Interleukin-10 / metabolism
  • Male
  • Odds Ratio
  • Polymorphism, Genetic*
  • Polymorphism, Single Nucleotide
  • Skin Tests
  • Transforming Growth Factor beta1 / genetics*

Substances

  • TGFB1 protein, human
  • Transforming Growth Factor beta1
  • Interleukin-10
  • Immunoglobulin E