Polymorphisms in Inflammasome Genes and Risk of Coal Workers' Pneumoconiosis in a Chinese Population

Abstract

BackgroundCoal workers' pneumoconiosis (CWP), resulting from the inhalation of silica-containing coal mine dust, is characterized by fibrosing nodular lesions that eventually develop into progressive pulmonary fibrosis. Recently, it has been hypothesized that inflammasomes could have a crucial role in the host response to silica and recent studies show that the inflammasome contributes to inflammation and pulmonary fibrosis. NLRP3, CARD8 are components of the NLRP3 inflammasome, which triggers caspase 1-mediated IL-1β and IL-18 release. In the present study, we investigated whether common single nucleotide polymorphisms (SNPs) in inflammasome genes are associated with CWP.MethodsWe performed an association study analyzing 3 NLRP3, 1 CARD8, 1 IL-1β, 2 IL-18 SNPs in a case-control study of 697 CWP and 694 controls. Genotyping was carried out by the TaqMan method.ResultsThe NLRP3 rs1539019 TT genotype was associated with a significantly increased risk of CWP (adjusted odds ratio (OR) = 1.39, 95% confidence interval (CI) = 1.07–1.81), compared with the GG/GT genotype, in particular among smokers (adjusted OR = 1.67, 95%CI = 1.15–2.42). In addition, the polymorphism was significantly associated with risk of CWP patients with stage I.ConclusionsThis is the first report showing an association between the NLRP3 rs1539019 polymorphism and CWP, and suggests that this polymorphism may confer increased risk for the development of the disease. Further studies are warranted to confirm our findings.

NLRP3 rs35829419 polymorphism is associated with increased susceptibility to multiple diseases in humans

“…The NACHT domain is a nucleotide binding domain, while LRR is a leucine-rich repeat domain used for detecting microbial pathogens, and PYD is useful for protein-protein interaction with the PYD of apoptosis-associated speck-like protein (ASC), which also contains a CARD domain; together these domains are important in assembly of the inflammasome multi-protein complex for mediating the inflammatory process and apoptosis signaling in response to various stimuli (Ji et al, 2012). Through PYD-PYD interactions, NLRP3 recruits ASC, which in turn leads to the assembly ofpro-caspase-1 through CARD-CARD interactions, and its subsequentactivation allows the maturation and release of IL-1β, causing widespread inflammatory reactions (Cummings et al, 2010).…”

Immune Recognition in Lung Diseases: Basic Research and Clinical Application

“…The silica or asbestos crystals engulfed by resident macrophages activated the NLRP3 inflammasome, leading to IL-1β production [73]. NLRP3 polymorphism appears to confer increased risk of pneumoconiosis in coal workers in Chinese population [74]. In contrast, NLRP3 is not critical in the development of asbestos-induced mesothelioma [75].…”

GITR promoter polymorphism contributes to risk of coal workers’ pneumoconiosis: A case–control study from China

“…A total of 13 SNPs were found, including nine common SNPs among Chinese population. The details of tSNP selection have been described in our previous study [2]. We selected three SNPs among those SNPs as probable candidates of functional polymorphisms.…”

“…As was reported in 2013, pneumoconiosis accounted for 87.72% of the total 23,152 reported occupational cases, among which over 50% had a strong relationship with coal-mining activities [1]. Coal worker's pneumoconiosis (CWP), originally thought to be a variant of silicosis, is one of the most common occupational respiratory diseases [2]. It makes up more than 60% of pneumoconiosis among Chinese workers [1].…”

“…prolonged lung inflammation and fibrotic nodular lesions that usually lead to progressive fibrosis [5]. Although silica dust exposure is recognized as the primary cause of pneumoconiosis, extensive researches indicate that genetic factors have played important roles in the development of pulmonary fibrosis [2,[6][7][8]. During the past four decades in China, CWP continues to occur even though work environment and prevention measures have been greatly improved [9], and still more than 23 million workers exposed to silica particles [10].…”