The Single Nucleotide Polymorphism Rs1814521 in Long Non-coding RNA ADGRG3 Associates with the Susceptibility to Silicosis: a Multi-stage Study

Overview

Journal Environ Health Prev Med

Specialties Environmental Health
Public Health

Date 2022 Mar 15

PMID 35289324

Authors

Wei Wang

Xiaofeng Chen

Chunping Li

Rui Zhao

Jinlong Zhang

Hong Qin

Miaomiao Wang

Yao Su

Minzhu Tang

Lei Han

Na Sun

Affiliations

Soon will be listed here.

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.

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