Dataset Information

Association between recent acetaminophen use and asthma: modification by polymorphism at TLR4.

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.

SUBMITTER: Lee SH

PROVIDER: S-EPMC4024959 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Association between recent acetaminophen use and asthma: modification by polymorphism at TLR4.

Lee Seung-Hwa SH Kang Mi-Jin MJ Yu Ho-Sung HS Hong Kyungmo K Jung Young-Ho YH Kim Hyung-Young HY Seo Ju-Hee JH Kwon Ji-Won JW Kim Byoung-Ju BJ Kim Ha-Jung HJ Kim Young-Joon YJ Kim Hee-Suk HS Kim Hyo Bin HB Park Kang Seo KS Lee So-Yeon SY Hong Soo-Jong SJ

Journal of Korean medical science 20140425 5

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 recru ...[more]

PMID: 24851022

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Project description:BACKGROUND:Epidemiologic studies have demonstrated associations between acetaminophen use and asthma. This investigation sought to determine whether sex modifies the acetaminophen-asthma association and whether leptin (LEP) and leptin receptor (LEPR) gene polymorphisms modulate the sex-specific associations. METHODS:Data from the Isle of Wight birth cohort (IOW; n?=?1456, aged 18 years) and Kuwait University Allergy (KUA; n?=?1154, aged 18-26 years) studies were analyzed. Acetaminophen use and current asthma were self-reported. Genotype information for eighteen polymorphisms in LEP and LEPR genes were available in the IOW study. Associations between acetaminophen use and asthma were stratified by sex and genotype. Poisson regression models with robust variance estimation were evaluated to estimate adjusted prevalence ratios (aPR) and 95% confidence intervals (CI). RESULTS:Acetaminophen use was dose-dependently associated with an increased prevalence of current asthma in the IOW and KUA studies. In both studies, sex-stratified analysis showed that acetaminophen use was associated with asthma among males, but not in females (Pinteraction?<? 0.05). Moreover, a sex- and genotype-stratified analysis of the IOW data indicated that acetaminophen was associated with asthma to a similar extent among males and females carrying two common alleles of LEPR polymorphisms. In contrast, among those carrying at least one copy of the minor allele of LEPR polymorphisms, the magnitude of association between acetaminophen use and asthma was pronounced among males (aPR?=?6.83, 95% CI: 2.87-16.24), but not among females (aPR?=?1.22, 95% CI: 0.61-2.45). CONCLUSIONS:The identified sex-related effect modification of the acetaminophen-asthma association varied across LEPR genotypes, indicating that the sex-specific association was confined to individuals with certain genetic susceptibility. If the acetaminophen-asthma association is causal, then our findings will aid susceptibility-based stratification of at-risk individuals and augment preventive public health efforts.

Dataset Information

Association between recent acetaminophen use and asthma: modification by polymorphism at TLR4.

Publications

Association between recent acetaminophen use and asthma: modification by polymorphism at TLR4.

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