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

Gao, Shu‐Qin; Wang, Yahong; Li, Chunyan; Yang, Liting; Zou, Baoan; Chen, Zuguang; Yao, Weimin; Song, Zeqing; Cheng, Junfen; Lin, Ziying; Liu, Gang

doi:10.1042/bsr20180410

Cited by 7 publications

(4 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Only 15-20% of smokers develop COPD, thereby suggesting that genetic, environmental or other as yet unknown factors contribute to the pathogenesis of COPD [96]. In addition, genetic polymorphisms of Ctss have been linked to a higher risk for COPD [97]. Therapeutic inhibition or genetic knockdown of CTSS reduced inflammation, epithelial apoptosis and lung damage in an IFNγ-induced model of emphysema [98].…”

Section: Chronic Obstructive Pulmonary Disease (Copd)mentioning

confidence: 99%

Cathepsin S: investigating an old player in lung disease pathogenesis, comorbidities, and potential therapeutics

et al. 2020

View full text Add to dashboard Cite

Dysregulated expression and activity of cathepsin S (CTSS), a lysosomal protease and a member of the cysteine cathepsin protease family, is linked to the pathogenesis of multiple diseases, including a number of conditions affecting the lungs. Extracellular CTSS has potent elastase activity and by processing cytokines and host defense proteins, it also plays a role in the regulation of inflammation. CTSS has also been linked to G-coupled protein receptor activation and possesses an important intracellular role in major histocompatibility complex class II antigen presentation. Modulated CTSS activity is also associated with pulmonary disease comorbidities, such as cancer, cardiovascular disease, and diabetes. CTSS is expressed in a wide variety of immune cells and is biologically active at neutral pH. Herein, we review the significance of CTSS signaling in pulmonary diseases and associated comorbidities. We also discuss CTSS as a plausible therapeutic target and describe recent and current clinical trials examining CTSS inhibition as a means for treatment. Proteases in pulmonary diseases Research in the last 60 years has demonstrated that proteases are critical contributors to pulmonary disease pathophysiology. Initially known as protein-degrading enzymes with a restricted spectrum of substrates, recent studies have revealed that the diversity of protease substrates and biological effects triggered by their processing is vast [1, 2]. Proteases are primarily known for their matrix degradation capabilities, but also play significant roles in other biological mechanisms such as angiogenesis, growth factor bioavailability, cytokine processing, receptor shedding and activation, as well as cellular processes including migration, proliferation, invasion, and survival [3]. Importantly, protease activity requires tight regulation, and disruption of the close interplay between proteases, substrates and inhibitors may contribute to the pathogenesis and progression of a variety of pulmonary diseases, including muco-inflammatory diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), as well as infection [4]. In pulmonary diseases with a high neutrophil burden such as CF, a protease:antiprotease imbalance is frequently observed. The activity of proteases such as neutrophil elastase (NE) in the respiratory tract is regulated by antiproteases, such as α1-antitrypsin (A1AT) [5], secretory leukoprotease inhibitor (SLPI) [6] and elafin [7]. However, in diseases like CF, the antiproteases are overburdened by their cognate proteases and this imbalance can result in chronic airway inflammation, decreased mucociliary clearance, mucus obstruction, extracellular matrix (ECM) remodeling, increased susceptibility to infection and impaired immune responses [8].

show abstract

Section: Chronic Obstructive Pulmonary Disease (Copd)mentioning

confidence: 99%

Cathepsin S: investigating an old player in lung disease pathogenesis, comorbidities, and potential therapeutics

et al. 2020

View full text Add to dashboard Cite

show abstract

“…In recent years, studies have shown that CTSS plays an important role in the occurrence and development of atherosclerosis, plaque vulnerability, rupture, and the occurrence of clinical complications [10]. CTSS is located on chromosome 1, 1q21, and its protein is a cysteine protease of papain superfamily and plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD) [11]. Some researchers found that CTSS gene polymorphisms are associated with obesity-related traits, and this association can be altered by dietary protein intake [12].…”

mentioning

confidence: 99%

Association between CTSS gene polymorphism and the risk of acute atherosclerotic cerebral infarction in Chinese population: a case–control study

2018

View full text Add to dashboard Cite

Objective: To investigate the association between the gene polymorphisms of rs774320676, rs768437857, rs928508030, and rs2275235 loci of Cathepsin S (CTSS) and risk of acute atherosclerotic cerebral infarction. Methods: A total of 315 patients with acute atherosclerotic cerebral infarction (study group) and 220 healthy subjects (control group) were enrolled in the present study. The genetic polymorphism of rs774320676, rs768437857, rs928508030, and rs2275235 loci of CTSS of subjects was analyzed by PCR-Sanger sequencing. Results: The proportion of carriers with mutant T allele at rs774320676 locus and mutant G allele at rs928508030 locus of CTSS in study group was significantly higher than the proportion in control group (P=0.000, adjusted odds ratio (OR) = 1.332, 95% confidence interval (CI) = 1.200–1.460; P<0.001, adjusted OR = 1.185, 95% CI = 1.055–1.314; P=0.002). The T allele at rs774320676 locus and the G allele at rs928508030 locus of CTSS were independent risk factors for acute atherosclerotic cerebral infarction (OR = 2.534, 95% CI = 1.020–4.652, P=0.006; OR = 2.016, 95% CI = 1.031–4.385, P=0.031). Conclusion: The single nucleotide polymorphisms (SNPs) of rs774320676 and rs928508030 of CTSS gene were related with risk for acute atherosclerotic cerebral infarction. The T allele at rs774320676 locus and G allele at rs928508030 locus of CTSS were genetic susceptibility genes of acute atherosclerotic cerebral infarction.

show abstract

“…[1][2][3] COPD is currently one of the major burdens on global health, and the prevalence of the disease among the elderly is about 10%, which is likely to become the third leading cause of death by 2030 in the world. 4,5 The pathogenesis of this disease involved in complex interactions among several factors which are mainly caused by long-term smoking, chronic infection, inhalation of industrial dust, and lacking of the body's own alpha-1-anti-trypsin. 6 Although smoking is a recognized risk factor for COPD, only a fraction of people who smoke end up with COPD.…”

Section: Introductionmentioning

confidence: 99%

SMAD4 rs10502913 is Significantly Associated with Chronic Obstructive Pulmonary Disease in a Chinese Han Population: A Case-Control Study

Hou¹,

Yuan²,

Wang³

et al. 2022

COPD

View full text Add to dashboard Cite

Background COPD is a respiratory disease caused by a combination of genetic and environmental factors. Polymorphism, as a genetic factor, can affect the susceptibility of the disease of COPD. In this study, we assessed the relationship between the polymorphisms of three genes and COPD risk in a Chinese Han population. Patients and Methods A total of 376 patients diagnosed with COPD and 284 control subjects were enrolled in this study. Multivariate logistic regression analysis was used to analyze the association between three polymorphisms (SMAD4 rs10502913, IL-4 rs2070874, HSPA1L rs2227956) and COPD susceptibility. Results The SMAD4 rs10502913 GG and AG genotype significantly increased COPD risk (adjusted OR = 2.235, 95% CI 1.198–4.104; adjusted OR = 2.218, 95% CI 1.204–4.151, respectively) compared with the AA genotype. In the stratification analyses, the GG genotype significantly increased the risk of COPD in subjects aged 60 and over (adjusted OR = 2.519, 95% CI 1.266–5.015) and with a smoking history of less than 30 years ( p =0.009; adjusted OR = 3.751; 95% CI 1.398–10.062). This increased risk was more pronounced in the group of GOLD I and GOLD II (adjusted OR = 3.628, 95% CI 1.022–12.885; adjusted OR = 2.394, 95% CI 1.004–5.710, respectively). In addition, AG genotype was associated with an increased COPD risk in subjects aged 60 and over (adjusted OR = 2.599, 95% CI 1.304–5.176) and in smokers ( p =0.021; adjusted OR = 2.269; 95% CI 1.132–4.548). This increased risk was more obvious in the group of GOLD III COPD ( p =0.047; adjusted OR = 2.532; 95% CI 1.012–6.336). Conclusion Our present study indicated that the genotype GG and AG of SMAD4 rs10502913 are associated with an increased risk of COPD in a Chinese Han population. Further validation studies with large-scale populations are needed to confirm our findings.

show abstract

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

Cited by 7 publications

References 35 publications

Cathepsin S: investigating an old player in lung disease pathogenesis, comorbidities, and potential therapeutics

Cathepsin S: investigating an old player in lung disease pathogenesis, comorbidities, and potential therapeutics

Association between CTSS gene polymorphism and the risk of acute atherosclerotic cerebral infarction in Chinese population: a case–control study

SMAD4 rs10502913 is Significantly Associated with Chronic Obstructive Pulmonary Disease in a Chinese Han Population: A Case-Control Study

Contact Info

Product

Resources

About