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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.    Electronic supplementary material  The online version of this article (10.1186/s12931-018-0892-y) contains supplementary material, which is available to authorized users.

respiratory research

Leptin receptor gene polymorphisms and sex modify the association between acetaminophen use and asthma among young adults: results from two observational studies