Related Experiment Video
Updated: Jun 25, 2026

Automated Measurement of Pulmonary Emphysema and Small Airway Remodeling in Cigarette Smoke-exposed Mice
Published on: January 16, 2015
A novel polymorphism in CDC6 is associated with the decline in lung function of ex-smokers in COPD
Noriaki Takabatake1, Sayumi Toriyama, Akira Igarashi
1Department of Pulmonary Medicine, Tohoku Central Hospital, Wagocho, Yamagata, Japan. ntakabatake@tohoku-ctr-hsp.com
Abstract:
The effect of smoking cessation on the rate of decline in lung function in patients with advanced stages of chronic obstructive pulmonary disease (COPD) has not been clarified. Saccharomyces cerevisiae cell division cycle 6 homolog (CDC6) protein possesses the pro-apoptotic properties. We tested our hypothesis that the individual susceptibility to rapid decline in lung function despite smoking cessation in patients with advanced stages of COPD is attributed to the genetic variants in the CDC6 gene. We prospectively followed 82 patients (ex-smokers) during 30months and evaluated the differences among the genotypes in the annual rate of decline in FEV(1.0) (%predicted) with ten single nucleotide polymorphisms (SNPs) in and around the CDC6 gene. We found significant differences in SNP5 (National Center for Biotechnology Information SNP reference: rs2077464), SNP6 (rs13706), SNP7 (rs7217852), and SNP8 (rs9904270) with a gene-dosage effect (ANOVA overall-P=0.029-0.030). The individual allele of SNP5G, SNP6A, SNP7G, and SNP8T were associated with rapid decline in FEV(1.0) (%predicted) [odds ratio (95% confidence interval)=2.35 (1.19-4.65), P=0.014]. The SNP5G/SNP6A/SNP7G/SNP8T haplotype was associated with an increased risk of deterioration of FEV(1.0) (%predicted) (P=0.017). Importantly, SNP6 caused a change in amino acids in CDC6 protein (Val441Ile), immediately upstream of the caspase-3-dependent cleavage site of CDC6 (Asp442) during apoptosis. These results suggest that CDC6 may be one of the susceptibility genes that contribute to rapid decline in lung function despite smoking cessation in these patients with COPD.
Related Concept Videos
COPD: Pathogenesis and Clinical Features
The primary cause for the onset of COPD is cigarette smoking and exposure to air pollution. These hazardous factors initiate a chain reaction within the lungs, resulting in chronic inflammation, damage to the airways, and a...
Chronic Obstructive Pulmonary Disease III: Chronic Bronchitis Features
Chronic Obstructive Pulmonary Disease-II: Pathophysiology
Chronic Inflammation
Chronic Obstructive Pulmonary Disease I: Introduction
Chronic Obstructive Pulmonary Disease II: Emphysema
Chronic Obstructive Pulmonary Disease-I: Introduction
