The rs2609255 polymorphism in the FAM13A gene is reproducibly associated with silicosis susceptibility in a Chinese population

Wang, Wei; Yu, Yuhui; Wu, Shuangshuang; Sang, Lingli; Wang, Xiaohui; Qiu, Anni; Yu, X.Y.; Li, Jingzhi; Yi, Min; Zheng, Huaping; Gao, Yuyan; Xiao, Jing; Lu, Yihua; Jiang, Liying; Lian, Yulong; Zhuang, Xun; Tian, Tian; Chu, Minjie

doi:10.1016/j.gene.2018.03.098

Cited by 15 publications

(11 citation statements)

References 27 publications

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“…The characteristics of the 177 SPF cases and 204 healthy workers recruited from Wuxi who were exposed to silica dust are entirely consistent with those of our previously published studies . Additional 126 SPF cases were recruited in 2017 from Datun Mining Business Group Co. Ltd. of Xuzhou in Jiangsu Province, with 126 healthy worker controls randomly selected from a pool of >1000 individuals with occupational dust exposure who participated in the routine health surveillance in 2017 in Xuzhou.…”

Section: Methodssupporting

confidence: 64%

miRNA sequencing reveals miRNA‐4508 from peripheral blood lymphocytes as potential diagnostic biomarker for silica‐related pulmonary fibrosis: A multistage study

Chu

Wang³

et al. 2019

Respirology

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Background and objective: This study aimed to identify miRNA as potential diagnostic biomarkers for silicarelated pulmonary fibrosis (SPF). Methods: We first performed a comprehensive miRNAseq screening in PBL of eight subjects exposed to silica dust (four individuals with SPF and four healthy controls). The promising miRNA were then evaluated in the first-stage validation using an independent GEO data set (GSE80555) of 6 subjects (3 individuals with SPF and 3 healthy controls), followed by a second-stage validation using 120 subjects exposed to silica dust (60 individuals with SPF and 60 healthy controls). Results: Thirty-five miRNA showed strong expression differences in miRNA-seq screening, while miRNA-4508 (P = 9.52 × 10 −3 ) was retained as a candidate after the first-stage validation (GSE80555), which was further confirmed in the second-stage validation with similar and strong effect (P = 9.93 × 10 −17 ). ROC analysis showed that miRNA-4508 could distinguish SPF cases from healthy controls with high AUC (0.886), with sensitivity of 81.7% and specificity of 86.7%. In addition, the miRNA-4508 upstream rs6576457 mutant A allele exhibited a strong association with susceptibility to SPF (OR = 1.64, 95% CI = 1.20-2.23, P = 0.002), while eQTL analysis revealed a potential association between different genotypes of rs6576457 and miRNA-4508 expression (P = 0.068) in 60 healthy subjects with silica dust exposure.Conclusion: miRNA-4508 may be a potential diagnostic marker for SPF, and rs6576457, a functional variant of miRNA-4508, may affect SPF susceptibility. The detailed mechanism of action of this miRNA remains to be elucidated. † Logistic regression analysis adjusted for age, gender, years of silica dust exposure and pack-years of smoking. miRNA, microRNA; OR, odds ratio; SNP, single nucleotide polymorphism.

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Section: Methodssupporting

confidence: 64%

miRNA sequencing reveals miRNA‐4508 from peripheral blood lymphocytes as potential diagnostic biomarker for silica‐related pulmonary fibrosis: A multistage study

Chu

Wang³

et al. 2019

Respirology

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“…The study including a total of 177 silicosis cases and 204 healthy worker controls matched on silica dust exposure years were analysed to assess associations between eight selected functional SNPs and the susceptibility of silicosis, which are entirely consistent with our previously published study 8 14. Furthermore, a two-stage case–control study matched by silica dust exposure years was designed to investigate the expression differences of the two genes ( CPM and CPSF6 ) between silicosis cases and healthy worker controls.…”

Section: Methodsmentioning

confidence: 79%

“…Silica dust exposure is a modifiable risk factor for silicosis, however, the fact that only a small fraction of workers exposed to silica dust will develop silicosis indicates that there may be non-modifiable risk factors associated with silicosis such as genetic predisposition 6 7. Thus, identifying key genes in which the alteration of expression or genetic variants (mainly single-nucleotide polymorphisms, SNPs) may enhance the development of silicosis may shed a light on the aetiology and underlying biological mechanisms of silicosis and might have crucial relevance to the identification of high-risk individuals with occupational silica dust exposure for intervention 8 9…”

Section: Introductionmentioning

confidence: 99%

Functional variant of the carboxypeptidase M (CPM) gene may affect silica-related pneumoconiosis susceptibility by its expression: a multistage case–control study

Chu

Wang³

et al. 2019

Occup Environ Med

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ObjectivesIn a genome-wide association study, we discovered chromosome 12q15 (defined as rs73329476) as a silica-related pneumoconiosis susceptibility region. However, the causal variants in this region have not yet been reported.MethodsWe systematically screened eight potentially functional single-neucleotide polymorphism (SNPs) in the genes near rs73329476 (carboxypeptidase M (CPM) and cleavage and polyadenylation specific factor 6 (CPSF6)) in a case–control study including 177 cases with silicosis and 204 healthy controls, matched to cases with years of silica dust exposure. We evaluated the associations between these eight SNPs and the development of silicosis. Luciferase reporter gene assays were performed to test the effects of selected SNP on the activity of CPM in the promoter. In addition, a two-stage case–control study was performed to investigate the expression differences of the two genes in peripheral blood leucocytes from a total of 64 cases with silicosis and 64 healthy controls with similar years of silica dust exposure as the cases.ResultsWe found a strong association between the mutant rs12812500 G allele and the susceptibility of silicosis (OR=1.45, 95% CI 1.03 to 2.04, p=0.034), while luciferase reporter gene assays indicated that the mutant G allele of rs12812500 is strongly associated with increased luciferase levels compared with the wild-type C allele (p<0.01). Moreover, the mRNA (peripheral blood leucocytes) expression of the CPM gene was significantly higher in subjects with silicosis compared with healthy controls.ConclusionsThe rs12812500 variant of the CPM gene may increase silicosis susceptibility by affecting the expression of CPM, which may contribute to silicosis susceptibility with biological plausibility.

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“…It could be that resins and other materials used in the manufacture of some products may lead to the generation of unexpected compounds, which effectively act as adjuvants to intensify the inflammatory response 39. Finally, silicosis pathogenesis should be viewed through a lens of gene‐environment interactions, with early reports confirming susceptibility to silicosis in carriers of polymorphisms in the TNF‐α and FAM13A genes 40…”

Section: Pathogenesismentioning

confidence: 99%

Silica‐related diseases in the modern world

Hoy

Chambers

2020

Allergy

243

174

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Silicosis is an ancient and potentially fatal pneumoconiosis caused by exposure to respirable crystalline silica. Silicosis is historically a disease of miners; however, failure to recognize and control the risk associated with silica exposure in contemporary work practices such as sandblasting denim jeans and manufacturing of artificial stone benchtops has led to re‐emergence of silicosis around the world. This review outlines the mineralogy, epidemiology, clinical and radiological features of the various forms of silicosis and other silica‐associated diseases. Perspective is provided on the most recent studies shedding light on pathogenesis, including the central role of innate immune effector cells and subsequent inflammatory cascades in propagating pulmonary fibrosis and the extrapulmonary manifestations, which uniquely characterize this pneumoconiosis. Clinical conundrums in differential diagnosis, particularly between silicosis and sarcoidosis, are highlighted, as is the importance of obtaining a careful occupational history in the patient presenting with pulmonary infiltrates and/or fibrosis. While silicosis is a completely preventable disease, unfortunately workers around the world continue to be affected and experience progressive or even fatal disease. Although no treatments have been proven, opportunities to intervene to prevent progressive disease, founded in a thorough cellular and molecular understanding of the immunopathology of silicosis, are highlighted.

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The rs2609255 polymorphism in the FAM13A gene is reproducibly associated with silicosis susceptibility in a Chinese population

Cited by 15 publications

References 27 publications

miRNA sequencing reveals miRNA‐4508 from peripheral blood lymphocytes as potential diagnostic biomarker for silica‐related pulmonary fibrosis: A multistage study

miRNA sequencing reveals miRNA‐4508 from peripheral blood lymphocytes as potential diagnostic biomarker for silica‐related pulmonary fibrosis: A multistage study

Functional variant of the carboxypeptidase M (CPM) gene may affect silica-related pneumoconiosis susceptibility by its expression: a multistage case–control study

Silica‐related diseases in the modern world

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