Gene-environment interaction between an IL4R variant and school endotoxin exposure contributes to asthma symptoms in inner-city children

Lai, Peggy S.; Massoud, Amir Hossein; Xia, Mingcan; Petty, Carter R.; Cunningham, Amparito; Chatila, Talal A.; Phipatanakul, Wanda

doi:10.1016/j.jaci.2017.08.023

Cited by 17 publications

(18 citation statements)

References 14 publications

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“…This research is also supported by an older study conducted by variant that results in a glutamine to arginine substitution at amino acid residue 576 (IL4Rα-Q576R polymorphism) has previously been associated with asthma diagnosis and severity (Rosa-Rosa, Zimmermann, Bernstein, Rothenberg, & Khurana Hershey, 1999). Lai et al (2018) have demonstrated that there is a gene-by environment interaction between the IL4Rα-Q576R polymorphism and environmental endotoxin exposure in school-aged children with asthma. (Lai et al, 2018).…”

Section: Genes and Asthma Health Outcomessupporting

confidence: 57%

Mold exposure levels in northeastern U.S. schools and homes : a quantitative examination of the difference in mold exposure levels between schools and homes & the asthma prevalence for a subset of northeastern U.S. schools among children ages 4 to 15

Howard¹

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Section: Genes and Asthma Health Outcomessupporting

confidence: 57%

Mold exposure levels in northeastern U.S. schools and homes : a quantitative examination of the difference in mold exposure levels between schools and homes & the asthma prevalence for a subset of northeastern U.S. schools among children ages 4 to 15

Howard¹

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“…For children not living on a farm, growing up with a cat or dog may have a protective effect against asthma symptoms [8•, 24••]. The mechanism of this effect is yet to be understood and it appears that genetics plays a role in asthma severity especially among ethnic minorities [72].…”

Section: Resultsmentioning

confidence: 99%

“…A human interleukin 4 receptor alpha chain gene (IL4R) variant that results in a glutamine to arginine substitution at amino acid residue 576 (IL4Rα-Q576R polymorphism) has previously been associated with asthma diagnosis and severity [71]. Lai et al [72] have demonstrated that there is a gene-byenvironment interaction between the IL4Rα-Q576R polymorphism and environmental endotoxin exposure in school-aged children with asthma. Higher classroom endotoxin levels were associated with fewer asthma symptoms for children with the Q/Q genotype (OR = 0.76 [0.55-1.04]), an equivocal effect for the Q/R genotype (OR = 1.10 [0.78-1.55]), and increased asthma symptoms for the R/R genotype (OR = 1.34 [0.85-2.13]) [72].…”

Section: Genes and Asthma Health Outcomesmentioning

confidence: 99%

“…Lai et al [72] have demonstrated that there is a gene-byenvironment interaction between the IL4Rα-Q576R polymorphism and environmental endotoxin exposure in school-aged children with asthma. Higher classroom endotoxin levels were associated with fewer asthma symptoms for children with the Q/Q genotype (OR = 0.76 [0.55-1.04]), an equivocal effect for the Q/R genotype (OR = 1.10 [0.78-1.55]), and increased asthma symptoms for the R/R genotype (OR = 1.34 [0.85-2.13]) [72]. In addition to genetics, exposure to animals, especially within the farm setting, has shown to play a role in asthma.…”

Section: Genes and Asthma Health Outcomesmentioning

confidence: 99%

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The Impact of Ambient Environmental Exposures to Microbial Products on Asthma Outcomes from Birth to Childhood

Howard

Orhurhu

Huang

et al. 2019

Curr Allergy Asthma Rep

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Purpose of Review Asthma is a chronic respiratory condition with increasing domestic and worldwide prevalence that burdens individuals and the healthcare system with high costs associated with long-term treatments and acute emergency room (ER) visits. It can be triggered by ambient microbes, including bacteria, viruses, and fungi. In this review, we examine the outcomes of asthma patients in relation to environmental exposures to ambient microbe products, focusing on whether exposure leads to asthma development from birth to childhood and if particular microbes are associated with worsened asthma exacerbations. Recent Findings Bacterial endotoxin is more prominent in homes with pets and may cause cytokine cascades that lead to asthma exacerbation. However, some studies have demonstrated a protective effect with early exposure. Patients with positive Aspergillus skin testing are more prone to moderate-severe or severe-uncontrolled asthma. Fungal sensitization is also associated with earlier onset of asthma and demonstrates a dose-dependent relationship of symptom severity and duration. Among viruses, rhinovirus has the greatest association with decreased lung function, severe asthma, and asthma-related hospital admissions. Distribution of microbial products and associated asthma symptoms depends on the geographical climate. Genetic variations among individuals also mitigate the effects of microbial products on asthma development and symptom severity. Summary Microbial products of bacteria, fungi, and viruses are associated with the development of asthma, more severe asthma symptoms, and worse outcomes. However, some early exposure studies have also demonstrated a protective effect. Bacterial and fungal products are related to decreased lung function and earlier onset of asthma. Viral products are related to asthma-associated hospital admissions; and the climate and patient genetics can also temper or intensify the relationships between microbial products, asthma development, and asthma symptom severity. Further research should focus on the effects of early microbe exposure and its interaction with human immune systems and asthma-related outcomes.

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“…The IL4Rα-Q576R polymorphism is associated with asthma prevalence and severity. The IL4Rα-Q576R genotype was recently found to be an effect modifier of the association between urban classroom endotoxin levels and asthma symptoms days 78 -demonstrating geneenvironment interaction.…”

Section: Geneticsmentioning

confidence: 99%

The Effects of the Environment on Asthma Disease Activity

Louisias

Ramadan

Naja

et al. 2019

Immunology and Allergy Clinics of North America

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Gene-environment interaction between an IL4R variant and school endotoxin exposure contributes to asthma symptoms in inner-city children

Cited by 17 publications

References 14 publications

Mold exposure levels in northeastern U.S. schools and homes : a quantitative examination of the difference in mold exposure levels between schools and homes & the asthma prevalence for a subset of northeastern U.S. schools among children ages 4 to 15

Mold exposure levels in northeastern U.S. schools and homes : a quantitative examination of the difference in mold exposure levels between schools and homes & the asthma prevalence for a subset of northeastern U.S. schools among children ages 4 to 15

The Impact of Ambient Environmental Exposures to Microbial Products on Asthma Outcomes from Birth to Childhood

The Effects of the Environment on Asthma Disease Activity

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