Gene expression of oxidative stress markers and lung function: A CARDIA lung study

Background: Circulating markers of oxidative stress have been associated with lower lung function. Our objective was to study the association of gene expression levels of oxidative stress pathway genes (ALOX12, ALOX15, ARG2, GSTT1, LPO, MPO, NDUFB3, PLA2G7, and SOD3) and lung function forced expiratory volume in one second (FEV₁), forced vital capacity (FVC) in Coronary Artery Risk Development in Young Adults study. Methods: Lung function was measured using spirometry and the Nanostring platform was used to estimate gene expression levels. Linear regression models were used to study association of lung function measured at year 30, 10-year decline in lung function and gene expression after adjustment for center, smoking, and BMI, measured at year 25. Results: The 10-year decline of FEV₁ was faster in highest NDUFB3 quartile compared to the lowest (difference = −2.09%; p = 0.001) after adjustment for multiple comparisons. The 10-year decline in FEV₁ and FVC was nominally slower in highest versus lowest quartile of PLA2G7 (difference = 1.14%; p = 0.02, and difference = 1.06%; p = 0.005, respectively). The other genes in the study were not associated with FEV₁ or FVC. Conclusion: Higher gene expression levels in oxidative stress pathway genes are associated with faster 10-year FEV₁ decline.