Transcriptome‐wide association study identifies PSMB9 as a susceptibility gene for coal workers' pneumoconiosis

Abstract

Coal workers' pneumoconiosis (CWP) is a type of typical occupational lung disease caused by prolonged inhalation of coal mine dust. The individuals' different genetic background may underlie their different susceptibility to develop pneumoconiosis, even under the same exposure level. This study aimed to identify susceptibility genes associated with CWP. Based on our previous genome-wide association study (GWAS, 202 CWP cases vs. 198 controls) and gene expression data obtained by analyzing human lungs and whole blood from the Genotype-Tissue Expression (GTEx) Portal, a transcriptome-wide association study (TWAS) was applied to identify CWP risk-related genes. Luciferase report gene assay, qRT-PCR, Western blot, immunofluorescence assay, and TUNEL assay were conducted to explore the potential role of the candidate gene in CWP. Proteasome 20S subunit beta 9 (PSMB9) was identified as a strong risk-related gene of CWP in both lungs and whole blood (Lungs: P TWAS = 4.22 Â 10 À4 ; Whole blood: P TWAS = 2.11 Â 10 À4 ). Single nucleotide polymorphisms (SNPs) rs2071480 and rs1351383, which locate in the promoter region and the first intron of the PSMB9 gene, were in high linkage disequilibrium (LD, r 2 = 0.98) with the best GWAS SNP rs4713600 (G>T, OR = 0.55, 95% CI: 0.42-0.74, P = 6.86 Â 10 À5 ). Both rs2071480 and rs1351383 significantly enhanced the transcriptional activity of PSMB9. Functional experiments revealed that silica exposure remarkably reduced the PSMB9 expression and caused cell apoptosis, while overexpression of PSMB9 markedly abolished silica-induced cell apoptosis. We here identified PSMB9 as a novel susceptibility gene for CWP and provided important insights into the further exploration of the CWP pathogenesis.

Genetic associations between circulating immune cells and periodontitis highlight the prospect of systemic immunoregulation in periodontal care

“…However, in the Genotype-Tissue Expression project (GTEx) database, we could not find transcriptome data related to oral tissues, such as gums, oral mucosa, and alveolar bone (Review Table 1). Owing to the limitations of the database, in the context of our study, we primarily relied on whole blood data, given its availability and the extensive precedent documented in the literature for its utilization (Xu et al, 2023;Yuan et al, 2022).…”

Inflammation and fibrosis in the coal dust-exposed lung described by confocal Raman spectroscopy

“…Coal workers’ pneumoconiosis (CWP) develops from inhaling coal dust or mineral dust particles. As of 2018, there were 97,500 reported occupational diseases in China, and 90% of them were pneumoconiosis ( Yuan et al, 2022 ). CWP patients have extensive fibrosis of the lung tissue, twisty, narrow, or distorted bronchi, and complications such as chronic obstructive pulmonary disease (COPD), which damages pulmonary function.…”