Gender-specific associations between polymorphisms in the Toll-like receptor (TLR) genes and lung function among...

Workers in swine operations are exposed to dust, bacteria, and virus, and are at increased risk of respiratory problems. Toll-like receptors (TLR) play an important role in human immune responses to respiratory hazards. Worker gender and age may significantly modify the involvement of TLR in the etiology of these respiratory outcomes. The aim of this study was to investigate whether modification effects of worker gender and age altered associations between polymorphisms in the TLR genes and lung function. This study included 374 full-time workers from large swine operations from Saskatchewan. Information on demography, lifestyle, pulmonary function,  and blood samples were obtained. Multiple linear regression and decision tree model were used in the analysis. Among females aged <45.8 years, workers with polymorphisms of rs4696480 in the TLR2 gene exhibited markedly better lung function than workers with wild-type. These associations were not observed among female workers aged ≥45.8 years and males. Among males, workers with polymorphisms of rs187084 in the TLR9 gene displayed significantly lower lung function than those with wild-type. This male-specific association was not dependent on worker age. This is the first study to report gender-specific correlations between lung function and polymorphisms of TLR genes, and modification effects of worker age on these associations, suggesting the importance of considering gender and age in genetic association studies of airway diseases due to exposure of high concentration of respiratory hazards.