NLRP3 and CARD8 polymorphisms influence risk for asbestos-related diseases

Abstract

Summary Background This study aimed to investigate the association between NLRP3 rs35829419 and CARD8 rs2043211 polymorphisms and the risk of developing pleural plaques, asbestosis, and malignant mesothelioma (MM), and to study the influence of the interactions between polymorphisms and asbestos exposure on the risk of developing these diseases. Methods The case-control study included 416 subjects with pleural plaques, 160 patients with asbestosis, 154 subjects with MM and 149 subjects with no asbestos disease. The NLRP3 rs35829419 and CARD8 rs2043211 polymorphisms were determined using real-time PCR-based methods. In the statistical analysis, standard descriptive statistics was followed by univariate and multivariate logistic regression modelling. Results Asbestos exposure (medium and high vs low) was associated with the risk for each studied asbestos-related disease. An increased risk of pleural plaques was found for CARD8 rs2043211 AT + TT genotypes (OR = 1.48, 95% CI 1.01–2.16, p = 0.042). When the analysis was performed for MM patients as cases, and pleural plaques patients as controls, a decreased MM risk was observed for carriers of CARD8 rs2043211 TT genotype (OR = 0.52, 95% CI 0.27–1.00, p = 0.049). The interactions between NLRP3 rs35829419 and CARD8 rs2043211 genotypes did not influence the risk of any asbestos-related disease. However, when testing interactions with asbestos exposure, a decreased risk of asbestosis was found for NLRP3 CA+AA genotypes (OR = 0.09, 95% CI 0.01–0.60, p = 0.014). Conclusions The results of our study suggest that NLRP3 and CARD8 polymorphisms could affect the risk of asbestos-related diseases.

Telomere length and TERT polymorphisms as biomarkers in asbestos-related diseases

“…Data on asbestos exposure were available from our previous studies. 30 A standardized questionnaire-based interview was conducted with cases having PP and control group to gather data on their smoking status, whereas data for patients with MM was extracted from medical records at The Institute of Oncology Ljubljana. 31 All participants were fully informed about the purpose of the study and willingly provided their informed written consent to participate.…”

The discovery of NLRP3 and its function in cryopyrin‐associated periodic syndromes and innate immunity

“…Beyond these disorders, the role of NLRP3 and its downstream effects through IL‐1 have been implicated in nearly every organ in humans. While some are perhaps more obvious given clear associations with known inflammasome triggers such as in silicosis 167 or asbestosis, 168 others such as neurodegenerative disorders 169 and ovarian aging 153 have been linked to excess NLRP3 activation and expression (Figure 8). For these challenging disorders, inhibitors of NLRP3 have been shown to reduce inflammation in vitro and in vivo, lending new opportunities for intervention.…”

Targeting the NLRP3 inflammasome and associated cytokines in scleroderma associated interstitial lung disease

“…Aberrant activation of the NLRP3 inflammasome has garnered significant interest for its potential pathogenic role in inflammatory conditions such as SSc-ILD. Genome-wide association studies have shown polymorphisms in the NLRP3 gene to be linked with the development of ILDs such as asbestosis (rs35829419) ( Franko et al, 2020 ), coal workers pneumoconiosis (rs1539019) ( Ji et al, 2012 ), and silicosis (rs1539019 and rs34298354) ( Weng et al, 2015 ); while specific NLRP3 polymorphisms have yet to be identified in SSc-ILD, further study in this arena could identify convergent molecular mechanisms linking divergent disease states. However, translational work completed by Artlett and colleagues demonstrated the connection between NLRP3 inflammasome activation and SSc by showing that dermal fibroblasts from SSc patients exhibit increased expression of inflammasome components, and that experimentally induced caspase-1 inhibition of both dermal and lung SSc fibroblasts ameliorated collagen deposition, reduced IL-1β and IL-18 secretion, and decreased αSMA (alpha smooth muscle actin) expression ( Artlett et al, 2011 ).…”