Association between recent acetaminophen use and asthma: modification by polymorphism at TLR4.
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.
Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea.
Seung-Hwa
SH
Lee
Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea.
Mi-Jin
MJ
Kang
Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea.
Ho-Sung
HS
Yu
Goucher College, Baltimore, MD, USA.
Kyungmo
K
Hong
Department of Pediatrics, Childhood Asthma Atopy Center, Research Center for Standardization of Allergic Disease, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Young-Ho
YH
Jung
Department of Pediatrics, Pusan National University Yangsan Hospital, Yangsan, Korea.
Hyung-Young
HY
Kim
Department of Pediatrics, Korea Cancer Center Hospital, Seoul, Korea.
Ju-Hee
JH
Seo
Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam, Korea.
Ji-Won
JW
Kwon
Department of Pediatrics, Inje University Haeundae Paik Hospital, Busan, Korea.
Byoung-Ju
BJ
Kim
Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea.
Ha-Jung
HJ
Kim
Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea.
Young-Joon
YJ
Kim
Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea.
Hee-Suk
HS
Kim
Department of Pediatrics, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea.
Hyo Bin
HB
Kim
Department of Pediatrics, Presbyterian Medical Center, Jeonju, Korea.
Kang Seo
KS
Park
Department of Pediatrics, Hallym University College of Medicine, Sacred Heart Hospital, Anyang, Korea.
So-Yeon
SY
Lee
Department of Pediatrics, Childhood Asthma Atopy Center, Research Center for Standardization of Allergic Disease, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Soo-Jong
0000-0003-1409-2113
SJ
Hong
D000082:Acetaminophen / Q000009:adverse effects* / Q000627:therapeutic use; D000293:Adolescent; D001249:Asthma / Q000139:chemically induced / Q000453:epidemiology / Q000235:genetics*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D003430:Cross-Sectional Studies; D004804:Eosinophils / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D020641:Polymorphism, Single Nucleotide; D017382:Reactive Oxygen Species / Q000276:immunology; D012306:Risk; D012307:Risk Factors; D011795:Surveys and Questionnaires; D051197:Toll-Like Receptor 4 / Q000235:genetics*
D017382:Reactive Oxygen Species; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D000082:Acetaminophen; D007073:Immunoglobulin E
Acetaminophen; Asthma; Bronchial Hyperresponsiveness; Gene-Environment Interaction; Toll-Like Receptor 4