Two CHRN susceptibility variants for COPD are genetic determinants of emphysema and chest computed tomography manifestations in Chinese patients.
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.
['Zhao|Zhuxiang|Z|', 'Jiang|Changbin|C|', 'Zhao|Dongxing|D|', 'Li|Yujun|Y|', 'Liang|Chunxiao|C|', 'Liu|Weifeng|W|', 'Wei|Shuquan|S|', 'Zhou|Yumin|Y|', 'Zhao|Ziwen|Z|', 'Ran|Pixin|P|']
D000368:Aged D000369:Aged, 80 and over D044466:Asians D016009:Chi-Square Distribution D002681:China D003430:Cross-Sectional Studies D005260:Female D005787:Gene Frequency D056726:Genetic Association Studies D020022:Genetic Predisposition to Disease D014644:Genetic Variation D006801:Humans D016015:Logistic Models D008168:Lung D008297:Male D008875:Middle Aged D061330:Multidetector Computed Tomography D016017:Odds Ratio D010641:Phenotype D011237:Predictive Value of Tests D065840:Protective Factors D029424:Pulmonary Disease, Chronic Obstructive D011656:Pulmonary Emphysema D011978:Receptors, Nicotinic D012307:Risk Factors D013147:Spirometry
COPD emphysema CT manifestation CHRN variant