Department of Occupational Health, Center for Disease Control and Prevention of Wuxi.
Department of Quality Management, Center for Disease Control and Prevention of Wuxi.
Environ Health Prev Med. 2022;27:5. doi: 10.1265/ehpm.21-00338.
This study aimed to evaluate the correlation between long non-coding RNA (lncRNA)-related single nucleotide polymorphisms (SNPs) and susceptibility to silicosis.
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.
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).
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.
本研究旨在评估长非编码 RNA（lncRNA）相关单核苷酸多态性（SNP）与矽肺易感性之间的相关性。
首先，对 8 名（矽肺病例 4 例，健康对照 4 例）暴露于二氧化硅粉尘的外周血淋巴细胞进行全面的 RNA 测序（RNA-seq）数据分析，以鉴定差异表达的 lncRNA（DE-lncRNA）。然后，使用多个数据库鉴定鉴定出的 DE-lncRNA 中的功能 SNP。最后，通过两阶段病例对照研究评估功能性 SNP 与矽肺易感性的关系。通过全基因组关联研究（GWAS）筛选 155 例矽肺病例和 141 例健康矽暴露对照的 SNP，通过改良多酶检测反应（iMLDR）系统基因分型验证 194 例矽肺病例和 235 例健康矽暴露对照的候选 SNP。
通过 RNA-seq 数据分析共鉴定出 76 个 DE-lncRNA（截止值：倍数变化>2 或倍数变化<0.5，P<0.05），通过多个公共数据库鉴定出这 76 个 DE-lncRNA 中的 127 个功能 SNP。此外，GWAS 筛选发现 5 个 SNP 与矽肺发病风险显著相关（P<0.05），而 GWAS 和 iMLDR 验证结果表明，rs1814521 的变异 A 等位基因与矽肺发病风险降低相关（OR=0.76，95%CI=0.62-0.94，P=0.011）。
lncRNA ADGRG3 中 SNP rs1814521 的存在与矽肺易感性相关。此外，在矽肺病例中发现 ADGRG3 表达水平较低。lncRNA ADGRG3 和 rs1814521 调节矽肺发生的潜在生物学机制需要进一步研究。
