A highly significant association between Cathepsin S gene polymorphisms rs12068264 and chronic obstructive pulmonary disease susceptibility in Han Chinese population.

Sheng-Lan Gao,Gang Liu,Zi-Ying Lin,Wei-Min Yao,Ze-Qing Song,La-Wei Yang,Chun-Yan Li,Jun-Fen Cheng,Zu-Guang Chen,Bao-An Zou,Ya-Hong Wang

doi:10.1042/bsr20180410

Abstract

Cathepsin S (CTSS) and Sirtuin-1 (SIRT1) played crucial roles in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the associations between the polymorphisms of CTSS as well as SIRT1 and COPD in Asian population remain elusive. In the present study, one single nucleotide polymorphism (SNP) in rs12068264 was discovered (in 385 individuals) to be associated with the susceptibility of COPD in a Chinese Han population. The genotyping was performed using improved multiplex ligase detection reaction (iMLDR) technique. Subjects with T allele of rs12068264 in CTSS gene had an increased risk of COPD (T compared with C: odds ratio (OR) = 1.351, 95% confidence interval (95% CI): 1.008–1.811, P=0.044) compared with C allele. Subjects with TT genotype at rs12068264 had a higher risk of COPD in a recessive model (TT compared with TC + CC: OR = 2.30, 95% CI: 1.06–4.989, P=0.035). Compared with the C variant of rs12068264, the homozygous carriers of the TT genotype had higher procalcitonin (PCT) levels. Finally, haplotype analysis demonstrated that the SNPs in the CTSS and SIRT1 gene had no statistical differences between patients with COPD and the controls. In conclusion, the genetic polymorphisms of CTSS were associated with the susceptibility of COPD in a Chinese Han population, which may be helpful in understanding genetic mechanisms underlying the pathogenesis of COPD.

Highlights

Chronic obstructive pulmonary disease (COPD) is a major cause of deaths worldwide and is characterized by an irreversible progressive decline in lung function and chronic inflammatory response [1]
The prevalence of rs12068264 T-allele frequencies in Cathepsin S (CTSS) gene was significantly higher in COPD patients than in controls (T compared with C: odds ratio (OR) = 1.351, 95% 95% confidence interval (CI): 1.008–1.811, P=0.044)
We found that rs12068264 of CTSS were associated with the risk of COPD in our population

Summary

Introduction

Chronic obstructive pulmonary disease (COPD) is a major cause of deaths worldwide and is characterized by an irreversible progressive decline in lung function and chronic inflammatory response [1]. Numerous studies demonstrated that oxidative stress, protease–antiprotease imbalance, as well as inflammation played important roles in COPD pathogenesis [3,4,5]. It is well reported that long-term exposure to cigarette smoke, a predominant risk stimuli for COPD development, leads to cellular oxidative stress and inflammatory response in the airways as well as lungs [3]. The molecular mechanisms underlying COPD pathogenesis are complex and it is very important to identify the genetic susceptibility factor of the development of COPD for early prevention, early detection, and the early treatment of this disease

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Conclusion