NLRP3 and CARD8 polymorphisms influence risk for asbestos-related diseases

Our plain-English summary of NLRP3 and CARD8 polymorphisms influence risk for asbestos-related diseases, by A. Franko, K. Goricar, V. Kovac, et al (Journal of Medical Biochemistry, 2020).

The study

• Authors: A. Franko, K. Goricar, V. Kovac, M. Dodic-Fikfak, V. Dolzan
• Journal: Journal of Medical Biochemistry
• Published: 2020;39(1):91-99
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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.

2020 Alenka Franko, Katja Goricar, Viljem Kovac, Metoda Dodic-Fikfak, Vita Dolzan, published by CEON/CEES.

In plain English

This case-control study from Slovenia examined whether two variations in genes for inflammation-related proteins, NLRP3 rs35829419 and CARD8 rs2043211, were linked to asbestos-related disease. It included 879 people: 416 with pleural plaques, 160 with asbestosis, 154 with malignant mesothelioma, and 149 occupationally exposed people with no asbestos disease. Genes were tested from blood samples. Cumulative asbestos exposure was grouped as low, medium or high, but reliable exposure data were available for only 81 of the mesothelioma patients. Medium and high exposure, compared with low, was associated with each disease. People with the CARD8 AT or TT genotype had higher odds of pleural plaques than those with AA (odds ratio 1.48, 95% CI 1.01–2.16). When mesothelioma patients were compared with pleural plaque patients, carriers of CARD8 TT had lower odds of mesothelioma (odds ratio 0.52, 95% CI 0.27–1.00). Among people with medium or high exposure, NLRP3 CA or AA carriers had lower odds of asbestosis (odds ratio 0.16, 95% CI 0.03–0.92). The authors concluded that these gene variations could affect the risk of asbestos-related diseases. They called for larger studies that also examine other variations in these genes.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Case-control study (genetic association study) using univariate and multivariate logistic regression
• Who was studied: 879 subjects in Slovenia: 416 with pleural plaques, 160 with asbestosis and 149 with no asbestos-related disease, all occupationally exposed and seen at the State Board for the Recognition of Occupational Asbestos Diseases (1998–2007); and 154 malignant mesothelioma patients treated at the Institute of Oncology Ljubljana (2004–2012). Of the 879, 645 were male and 234 female.
• Exposure: Occupational asbestos exposure (fiber types not specified in this article), grouped by cumulative exposure as low (under 11 fibres/cm3-years), medium (11–20) or high (over 20). For most mesothelioma patients, exposure was estimated from work history. The genetic variations studied were NLRP3 rs35829419 and CARD8 rs2043211.
• Main results:
  • Medium and high asbestos exposure, compared with low, was associated with each disease studied. Odds ratios (Table II): pleural plaques vs no disease 1.73 (95% CI 1.08–2.77); asbestosis vs no disease 4.08 (2.43–6.87); mesothelioma vs no disease 5.11 (2.80–9.3); mesothelioma vs pleural plaques 2.95 (1.81–4.81).
  • Compared with the CARD8 rs2043211 AA genotype, AT + TT genotypes were associated with increased risk of pleural plaques (pleural plaques vs no disease, univariate): OR 1.48, 95% CI 1.01–2.16, p = 0.042.
  • With mesothelioma patients as cases and pleural plaque patients as controls, carriers of the CARD8 TT genotype had a decreased risk of mesothelioma: OR 0.52, 95% CI 0.27–1.00, p = 0.049.
  • No association was found between CARD8 genotypes and the other disease comparisons, or between NLRP3 genotypes and any of the diseases, in the main analysis.
  • The authors reported that the results did not change considerably after adjustment. In the adjusted analysis (Table VI), the pleural plaques OR for CARD8 AT+TT was 1.46 (95% CI 1.00–2.13, p = 0.052). For mesothelioma vs pleural plaques, the CARD8 TT OR was 0.37 (0.14–0.96, p = 0.040).
  • Interactions between the NLRP3 and CARD8 genotypes did not influence the risk of any asbestos-related disease.
  • There was a multiplicative interaction between NLRP3 rs35829419 and asbestos exposure for asbestosis (OR 0.09, CI 0.01–0.60, p = 0.014). Among subjects with medium or high exposure, NLRP3 CA + AA genotypes were associated with decreased asbestosis risk: OR 0.16, CI 0.03–0.92, p = 0.040. This subgroup included 4 no-disease subjects and 2 asbestosis patients with CA+AA genotypes (Table VII).
• The authors' conclusion: The authors concluded that NLRP3 and CARD8 polymorphisms could affect the risk of asbestos-related diseases.
• Limitations the authors state:
  • Reliable semi-quantitative asbestos exposure data could be obtained for only 81 of the 154 mesothelioma patients.
  • The CARD8 variant studied represents only a fraction of the variation in the CARD8 gene, so other variants need investigation.
  • The authors stated that further studies with more subjects and other NLRP3 and CARD8 polymorphisms are needed to clarify the associations.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Plaques, Malignant Mesothelioma, Asbestos Exposure, Case-Control Study.

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