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Leptin receptor gene polymorphisms and sex modify the association between acetaminophen use and asthma among young adults: Results from two observational studies 11 Medical and Health Sciences 1117 Public Health and Health Services 06 Biological Sciences 0604 Genetics

Leptin receptor gene polymorphisms and sex modify the association between acetaminophen use and asthma among young adults: Results from two observational studies 11 Medical and Health Sciences 1117 Public Health and Health Services 06 Biological Sciences 0604 Genetics
Leptin receptor gene polymorphisms and sex modify the association between acetaminophen use and asthma among young adults: Results from two observational studies 11 Medical and Health Sciences 1117 Public Health and Health Services 06 Biological Sciences 0604 Genetics

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 (P interaction < 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.

Acetaminophen, Asthma, Epidemiology, Leptin, Sex
1465-9921
Ziyab, Ali H.
12905e44-3fd1-47c2-98e5-35320e89815b
Mukherjee, Nandini
f64f02d6-2fd0-40db-88ee-5f85b59b8e0b
Kurukulaaratchy, Ramesh J.
9c7b8105-2892-49f2-8775-54d4961e3e74
Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
Ewart, Susan
28667421-3cf7-43d7-b1c3-ca27564938f7
Arshad, Hasan
917e246d-2e60-472f-8d30-94b01ef28958
Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853
Ziyab, Ali H.
12905e44-3fd1-47c2-98e5-35320e89815b
Mukherjee, Nandini
f64f02d6-2fd0-40db-88ee-5f85b59b8e0b
Kurukulaaratchy, Ramesh J.
9c7b8105-2892-49f2-8775-54d4961e3e74
Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
Ewart, Susan
28667421-3cf7-43d7-b1c3-ca27564938f7
Arshad, Hasan
917e246d-2e60-472f-8d30-94b01ef28958
Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853

Ziyab, Ali H., Mukherjee, Nandini, Kurukulaaratchy, Ramesh J., Zhang, Hongmei, Ewart, Susan, Arshad, Hasan and Karmaus, Wilfried (2018) Leptin receptor gene polymorphisms and sex modify the association between acetaminophen use and asthma among young adults: Results from two observational studies 11 Medical and Health Sciences 1117 Public Health and Health Services 06 Biological Sciences 0604 Genetics. Respiratory Research, 19 (1), [179]. (doi:10.1186/s12931-018-0892-y).

Record type: Article

Abstract

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 (P interaction < 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.

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Accepted/In Press date: 13 September 2018
e-pub ahead of print date: 19 September 2018
Published date: 19 September 2018
Keywords: Acetaminophen, Asthma, Epidemiology, Leptin, Sex

Identifiers

Local EPrints ID: 423856
URI: http://eprints.soton.ac.uk/id/eprint/423856
ISSN: 1465-9921
PURE UUID: 38962c41-be09-4792-8329-c0c81d23efca
ORCID for Ramesh J. Kurukulaaratchy: ORCID iD orcid.org/0000-0002-1588-2400

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Date deposited: 03 Oct 2018 16:30
Last modified: 16 Mar 2024 03:09

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Contributors

Author: Ali H. Ziyab
Author: Nandini Mukherjee
Author: Hongmei Zhang
Author: Susan Ewart
Author: Hasan Arshad
Author: Wilfried Karmaus

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