The single nucleotide polymorphism rs1814521 in long non-coding RNA <i>ADGRG3</i> associates with the susceptibility to silicosis: a multi-stage study

Abstract

Background: This study aimed to evaluate the correlation between long non-coding RNA (lncRNA)-related single nucleotide polymorphisms (SNPs) and susceptibility to silicosis. Methods: First, RNA-sequencing (RNA-seq) data were comprehensively analyzed in the peripheral blood lymphocytes of eight participants (four silicosis cases and four healthy controls) exposed to silica dust to identify differentially expressed lncRNAs (DE-lncRNAs). The functional SNPs in the identified DE-lncRNAs were then identified using several databases. Finally, the association between functional SNPs and susceptibility to silicosis was evaluated by a two-stage case-control study. The SNPs of 155 silicosis cases and 141 healthy silica-exposed controls were screened by genome-wide association study (GWAS), and the candidate SNPs of 194 silicosis cases and 235 healthy silica-exposed controls were validated by genotyping using the improved Mutiligase Detection Reaction (iMLDR) system. Results: A total of 76 DE-lncRNAs were identified by RNA-seq data analysis (cut-offs: fold change > 2 or fold change < 0.5, P < 0.05), while 127 functional SNPs among those 76 DE-lncRNAs were identified through multiple public databases. Furthermore, five SNPs were found to be significantly correlated with the risk of silicosis by GWAS screening (P < 0.05), while the results of GWAS and iMLDR validation indicated that the variant A allele of rs1814521 was associated with a reduced risk of silicosis (OR = 0.76, 95% CI = 0.62-0.94, P = 0.011). Conclusion:The presence of the SNP rs1814521 in the lncRNA ADGRG3 is associated with susceptibility to silicosis. Moreover, ADGRG3 was found to be lowly expressed in silicosis cases. The underlying biological mechanisms by which lncRNA ADGRG3 and rs1814521 regulate the development of silicosis need further study.

Epidemiology of occupational diseases in Romania and Israel: silicosis as a national concern

“…[6] Some exposed individuals may be more susceptible than others to develop the disease, due to the genetic polymorphism of long non-coding RNA (lncRNA)-related single nucleotide. [7] Experimental studies confirm the early onset of oxidative damage in rats and culture cell model for silicosis, progressively evolving from the inflammatory stage to fibrosis. [8,9] Cellular damage results mainly in the generation of free radicals and the release of cytokines.…”

From Engineered Stone Slab to Silicosis: A Synthesis of Exposure Science and Medical Evidence

“…Seven circular RNA -SNPs were identified, with variant A of rs17115143 (an allele located on SNHG14 ) being found to have a strong association with silicosis risk in the validation study (OR = 1.68, p = 0.032) [ 77 ]. SNPs in long non-coding RNA (lncRNA) were also screened using (GWAS) in relation to the risk of silicosis [ 78 ]. The variant A allele of rs1814521 in the lncRNA ADGRG3 was associated with a reduced risk of silicosis (OR = 0.76, 95% CI = 0.62–0.94, p = 0.011), aligned with the observation that ADGRG3 was down-regulated in silicosis cases [ 78 ].…”

“…SNPs in long non-coding RNA (lncRNA) were also screened using (GWAS) in relation to the risk of silicosis [ 78 ]. The variant A allele of rs1814521 in the lncRNA ADGRG3 was associated with a reduced risk of silicosis (OR = 0.76, 95% CI = 0.62–0.94, p = 0.011), aligned with the observation that ADGRG3 was down-regulated in silicosis cases [ 78 ]. However, these genetic association studies have been performed in a single population, and more studies are required to replicate these findings in different ethnic cohorts with a focus on stone benchtop industry workers.…”

The emerging role of epigenetic regulation in the progression of silicosis

“…Ma et al found that the expression of lncRNA-ATB was upregulated in the plasma of coal miners and was positively correlated with the concentration of TGF-β [ 86 ]. Besides, the RNA-sequencing data were comprehensively analyzed in the peripheral blood lymphocytes of eight participants (four silicosis cases vs. four healthy controls), the results showed that the expression of lncRNA ADGRG3 was low in silicosis patients, and the relevant mechanism might be that single nucleotide polymorphisms rs1814521 in lncRNA ADGRG3 was associated with the susceptibility of silicosis [ 87 ] (Table 2 ).…”