4.5 Article

Effect of early-life antibiotic exposure and IL-13 polymorphism on atopic dermatitis phenotype

Journal

PEDIATRIC ALLERGY AND IMMUNOLOGY
Volume 32, Issue 7, Pages 1445-1454

Publisher

WILEY
DOI: 10.1111/pai.13531

Keywords

antibacterial agents; atopic; dermatitis; interleukin-13; phenotype; polymorphism

Funding

  1. Korea Disease Control and Prevention Agency [2008-E33030-00, 2009-E33033-00, 2011-E33021-00, 2012-E33012-00, 2013-E51003-00, 2014-E51004-00, 2014-E51004-01, 2014-E51004-02, 2017-E67002-00, 2017-E67002-01, 2017-E67002-02]
  2. Bio & Medical Technology Development Program of the National Research Foundation (NRF) - Korean government (MSIT) [2017M3A9F3043834]

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Exposure to antibiotics within 6 months of age was associated with an increased risk of developing early-persistent atopic dermatitis (AD) within 3 years of life, with the risk being dose-dependent. There was a weak interaction between genetic polymorphisms and environmental factors in the development of AD. Children with specific genetic variations had a higher risk of developing early-persistent AD when exposed to antibiotics multiple times compared to those without such exposure.
Background: Although atopic dermatitis (AD) is associated with certain gene variants, the rapidly increasing incidence of AD suggests that environmental factors contribute to disease development. In this study, we investigated the association of AD incidence and phenotype with antibiotic exposure within 6 months of age, considering the dose administered and genetic risk. Methods: This study included 1637 children from the COCOA cohort. Pediatric allergists assessed the presence of AD at each visit and obtained information about antibiotic exposure for more than 3 days. IL-13 (rs20541) polymorphism was genotyped by the TaqMan method. We stratified the AD phenotypes into four groups and used multinomial logistic regression models for analysis. Results: Antibiotic exposure within 6 months of age was found to increase the risk of AD within 3 years of life (aOR = 1.40; 95% CI, 1.09-1.81) in dose-dependent manner. Antibiotic exposure more than twice increased the risk of the early-persistent AD phenotype (aOR = 2.50; 95% CI, 1.35-4.63). There was a weak interaction between genetic polymorphisms and environmental factors on the development of AD (p for interaction = 0.06). Children with the IL-13 (rs20541) GA + AA genotype have a higher risk of the early-persistent AD phenotype when exposed to antibiotics more than twice than those with the IL-13 (rs20541) GG genotype and without exposure to antibiotics (aOR = 4.73; 95% CI, 2.01-11.14). Conclusion: Antibiotic exposure within 6 months was related to the incidence of early-persistent AD and a dose-dependent increase in the incidence of AD in childhood, whose effect was modified by the IL-13 (rs20541) genotype.

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