Genetic variability of immune checkpoints in asbestos-related diseases

Abstract

Background. Asbestos exposure is associated with asbestos-related diseases such as pleural plaques, asbestosis, lung cancer, malignant mesothelioma (MM), as well as several other types of cancer. Although the exact mechanism underlying asbestos-related diseases is not yet fully understood, the immune system may play an important role. Immune checkpoints such as programmed cell death receptor 1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) regulate immune responses and are crucial for maintaining immune tolerance, while defects in these mechanisms can lead to the development of cancer. The aim of present study was to investigate the association of polymorphisms in the immune checkpoint genes for PD-1 (PDCD1), PD-L1 (CD274), and CTLA-4 (CTLA4) with the risk of asbestos-related diseases.

Subjects and methods. We conducted a retrospective case-control study. The cases included individuals with asbestosis or pleural plaques and MM patients. The controls were asbestos-exposed subjects who did not develop asbestos-related diseases. All subjects were genotyped for PDCD1 (rs2227982, rs222798, rs10204525), CD274 (rs2297136, rs4143815, rs4742098) and CTLA4 (rs5742909, rs4553808, rs231775) polymorphisms using competitive allele-specific PCR. Statistical analysis was performed with logistic and Cox regression methods.

Results. Our study showed that the The other investigated polymorphisms were not associated with any of the asbestos-related diseases.

Conclusions. CTLA4 polymorphisms may play a role in the susceptibility for asbestos-related diseases in asbestos. Our results may contribute to a better understanding of the pathogenesis and progression of asbestos-related diseases.

Keywords: asbestos, malignant mesothelioma, immune checkpoints, polymorphism of one nucleotide