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

Authors Zhao Z, Jiang C, Zhao D, Li Y, Liang CX, Liu W, Wei S, Zhou Y, Zhao Z, Ran P

Received 6 February 2017

Accepted for publication 19 April 2017

Published 15 May 2017 Volume 2017:12 Pages 1447—1455

DOI https://doi.org/10.2147/COPD.S134010

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Charles Downs

Peer reviewer comments 3

Editor who approved publication: Dr Richard Russell

Zhuxiang Zhao,1,2 Changbin Jiang,1 Dongxing Zhao,1 Yujun Li,2 Chunxiao Liang,1 Weifeng Liu,2 Shuquan Wei,2 Yumin Zhou,1 Ziwen Zhao,2 Pixin Ran1

1The State Key Laboratory of Respiratory Diseases, The First Affliated Hospital, Guangzhou Medical University, Guangzhou, 2The Pulmonary Medicine,Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China

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

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