Abstract
Activation of toll-like receptors (TLR1, TLR5, TLR6) and downstream markers (CCR1, MAPK14, ICAM1) leads to increased systemic inflammation. Our objective was to study the association between the gene expression levels of these six genes and lung function (Forced Expiratory Volume in one second (FEV1), Forced Vital Capacity (FVC) and FEV1/FVC). We studied gene expression levels and lung function in the Coronary Artery Risk Development in Young Adults study. Spirometry testing was used to measure lung function and gene expression levels were measured using the Nanostring platform. Multivariate linear regression models were used to study the association between lung function measured at year 30, 10-year decline from year 20 to year 30, and gene expression levels (highest quartile divided into two levels – 75th to 95th and>95th to 100th percentile) adjusting for center, smoking and BMI, measured at year 25. Year 30 FEV1 and FVC were lower in the highest level of TLR5 compared to the lowest quartile with difference of 4.00% (p for trend: 0.04) and 3.90% (p for trend: 0.05), respectively. The 10-year decline of FEV1 was faster in the highest level of CCR1 as compared to the lowest quartile with a difference of 1.69% (p for trend: 0.01). There was no association between gene expression and FEV1/FVC. Higher gene expression levels in TLR5 and CCR1 are associated with lower lung function and faster decline in FEV1 over 10 years, in a threshold manner, providing new insights into the role of inflammation in lung function.
Highlights
Biomarkers of systemic inflammation such as C-reactive protein (CRP) and fibrinogen have been associated with lower FEV1 and FVC, chronic obstructive pulmonary disease (COPD) and asthma[1,2,3,4,5,6]
We evaluated the association between lung function at Coronary Artery Risk Development in Young Adults (CARDIA) exam years 30, 10-year decline in lung function and year 25 gene expression levels of TLR5, MAPK14 and CCR1 using linear regression models after adjustment for center, smoking status and body mass index (BMI)
The scatterplots of the gene expressions showed a wide range of the distribution of the gene expression levels for all six genes, with and highest correlation seen between TLR1 and TLR6 (r = 0.73; p-
Summary
Biomarkers of systemic inflammation such as C-reactive protein (CRP) and fibrinogen have been associated with lower FEV1 and FVC, chronic obstructive pulmonary disease (COPD) and asthma[1,2,3,4,5,6]. These are non-specific inflammatory biomarkers that do not help elucidate the underlying biological pathways that increase systemic inflammation. A better understanding of specific biological pathways that modulate down-stream inflammatory markers such as CRP may be useful in understanding the pathogenesis of pulmonary diseases such as COPD and asthma. We hypothesized that higher gene expression level of biomarkers associated with increased inflammation would be associated with a lower lung function measurement, and with a faster decline in lung function
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