Differential Expression of Vitamin E and Selenium-Responsive Genes by Disease Severity in Chronic Obstructive Pulmonary Disease

Abstract

Antioxidant nutritional status is hypothesized to influence chronic obstructive pulmonary disease (COPD) susceptibility and progression. Although past studies relate antioxidants to gene expression, there are no data in patients with COPD. This study investigated the hypothesis that antioxidant status is compromised in patients with COPD, and antioxidant-responsive genes differentially express in a similar pattern. Lung tissue samples from patients with COPD were assayed for vitamin E and gene expression. Selenium and vitamin E were assayed in corresponding plasma samples. Discovery based genome-wide expression analysis compared moderate, severe, and very severe COPD (GOLD II-IV) patients to mild and at-risk/normal (GOLD 0-I). Hypotheses-driven analyses assessed differential gene expression by disease severity for vitamin E-responsive and selenium-responsive genes. GOLD II-IV COPD patients had 30% lower lung tissue vitamin E levels compared to GOLD 0-I participants (p = 0.0082). No statistically significant genome-wide differences in expression by disease severity were identified. Hypothesis-driven analyses of 109 genes found 16 genes differentially expressed (padjusted<0.05) by disease severity including 6 selenium-responsive genes (range in fold-change -1.39 to 2.25), 6 vitamin E-responsive genes (fold-change -2.30 to 1.51), and 4 COPD-associated genes. Lung tissue vitamin E in patients with COPD was associated with disease severity and vitamin E-responsive genes were differentially expressed by disease severity. While nutritional status is hypothesized to contribute to COPD risk, and is of therapeutic interest, evidence to date is mainly observational. The findings reported herein are novel, and support a role of vitamin E in COPD progression.

Nutritional immunity: the impact of metals on lung immune cells and the airway microbiome during chronic respiratory disease

“…However, whether or not copper levels in lung immune cells dictate function or regulate responses to cigarette smoke remains to be determined. Finally, selenium responsive genes are altered in individuals with COPD [ 339 ] and COPD patients with higher selenium have a higher FEV1 [ 340 ]. Selenium and manganese levels may be beneficial before the clinical onset of COPD in smokers [ 341 ] and manganese levels are higher in COPD patients with severe disease when compared to control smokers [ 342 ] however the role of selenium or manganese in disease pathogenesis is unknown.…”

Common Risk Factor Approach to Limit Noncommunicable Diseases and Periodontal Disease—The Molecular and Cellular Basis

“…Vitamin E and Vitamin C can affect the lipid peroxidation chain reaction and protect the lung against oxidative damage. [ 66 ] Vitamins E and C can also protect DNA and prevent tumor initiation. Vitamin K forms a prerequisite for the formation of coagulation factors and is important for the formation of proteins osteocalcin and periostin, which are essential for bone metabolism.…”

Early chronic obstructive pulmonary disease: A new perspective

“… 72 8-isoprostanes, glucose-regulated protein 78 (GRP78), CD163, and transglutaminase-2 in lung tissue, sputum, and plasma from patients with COPD were also associated with decreased lung function. 73 , 74 , 75 , 76 , 77 Due to the limitations in methods of detection, several biomarkers of early COPD are still in the research stage and need to be confirmed by further studies.…”