J Korean Med Sci.  2014 May;29(5):662-668. 10.3346/jkms.2014.29.5.662.

Association between Recent Acetaminophen Use and Asthma: Modification by Polymorphism at TLR4

• Lee SH
• Kang MJ
• Yu HS
• Hong K
• Jung YH
• Kim HY
• Seo JH
• Kwon JW
• Kim BJ
• Kim HJ
• Kim YJ
• Kim HS
• Kim HB
• Park KS
• Lee SY
• Hong SJ

• KMID: 1786107
• DOI: http://doi.org/10.3346/jkms.2014.29.5.662

Abstract

The risk of asthma has been increasing in parallel with use of acetaminophen, which is a potential source of oxidative stress. Toll-like receptor 4 (TLR4) plays a critical role not only in innate immunity, but also in mediating reactive oxygen species induced inflammation. Therefore, we investigated associations between acetaminophen usage and TLR4 polymorphism on asthma and bronchial hyperresponsiveness (BHR). The number of 2,428 elementary school children in Seoul and Jeongeup cities was recruited. Subjects who used acetaminophen with a family history of asthma had an increased risk of both asthma diagnosis ever and current asthma. Individuals with CT+TT genotypes at the TLR4 polymorphism, in combination with acetaminophen usage, also demonstrated an increased risk of asthma diagnosis ever (aOR, 2.08; 95% confidence interval [CI], 1.10-3.92). Family history of asthma and acetaminophen usage were risk factors for BHR. Although TLR4 was not an independent risk factor for BHR, individuals with CT+TT genotypes at the TLR4 polymorphism had an increased risk of BHR when combined with acetaminophen usage (aOR, 1.74; 95% CI, 1.03-2.94). In conclusion, acetaminophen usage may be associated with asthma and BHR in genetically susceptible subjects. This effect may be modified by polymorphism at TLR4.

Keyword

Acetaminophen; Asthma; Bronchial Hyperresponsiveness; Toll-Like Receptor 4; Gene-Environment Interaction

MeSH Terms

Acetaminophen/*adverse effects/therapeutic use
Adolescent
Asthma/chemically induced/epidemiology/*genetics
Bronchial Hyperreactivity/chemically induced/epidemiology/*genetics
Child
Cross-Sectional Studies
Eosinophils/immunology
Female
Genetic Predisposition to Disease
Genotype
Humans
Immunoglobulin E/blood/immunology
Inflammation/immunology
Male
Oxidative Stress/drug effects
Polymorphism, Single Nucleotide
Questionnaires
Reactive Oxygen Species/immunology
Risk
Risk Factors
Toll-Like Receptor 4/*genetics
Acetaminophen
Reactive Oxygen Species
Immunoglobulin E
Toll-Like Receptor 4

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