Two CHRN susceptibility variants for COPD are genetic determinants of emphysema and chest computed tomography manifestations in Chinese patients

Abstract

Quantitative computed tomography (CT) measures of emphysema have been shown to be associated with increased mortality in humans, but genetic variants affecting the quantitative parameters of chest CT that measure degree of emphysema have not yet been examined. In this study, using available chest CT data from a total of 344 emphysema patients, we assessed the correlations between five chronic obstructive pulmonary disease (COPD) susceptibility variants in the cholinergic receptor nicotinic (CHRN) genes and the degree of emphysema and chest CT manifestations. We verified that most of the parameters were significantly correlated with the degree of emphysema. Compared to rs76071148AA and TT genotype carriers, the rs76071148AT genotype carriers exhibited a decreased probability of having severe emphysema (odds ratio [OR] =0.63, 95% confidence interval [CI] =0.40–0.99), whereas the variant rs8040868C allele was negatively correlated with the emphysema index (P=0.002). Interestingly, further stratification analysis grouped by spirometry-diagnosed COPD status revealed that the variant rs8040868C (CT + CC) genotypes exerted a protective effect against severe emphysema with borderline significance (OR =0.41, 95% CI =0.16–1.05) and affected the mean lung density, emphysema index, ratio of airway wall thickness to airway dimensions (AWT/AD), and AWT grade in spirometry-diagnosed non-COPD subjects. The rs76071148 variant was also significantly associated with AWT/AD and AWT grade in those individuals. In summary, we determined that rs8040868 and rs76071148 are promising indicators of the degree of emphysema and chest CT manifestations, especially in spirometry-diagnosed non-COPD subjects.

Keywords:

• COPD
• CHRN variant
• CT manifestation
• emphysema

Supplementary material

Table S1 Distributions of CHRN variants and their associations with degree of emphysema stratified by spirometry-diagnosed COPD status

Acknowledgments

The authors thank everyone who participated in this study and its funders. In particular, they also thank Hua He (The First Affiliated Municipal Hospital, Guangzhou Medical University) and Wei Hong (The State Key Laboratory of Respiratory Diseases, The First Affiliated Hospital, Guangzhou Medical University) for their help with monitoring, data collection, and conducting the statistical analysis.

This work was supported by the National Natural Science Foundation of China (81170043) and the Science and Technology Project of Guangdong (2013B021800069). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Disclosure

The authors report no conflicts of interest in this work.