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

Wei Wang; Xiaofeng Chen; Chunping LI; Rui Zhao; Jinlong Zhang; Hong Qin; Miaomiao Wang; Yao SU; Minzhu Tang; Lei Han; Na Sun

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

Author: Wei WANG ¹ ; Xiaofeng CHEN ² ; Chunping LI ¹ ; Rui ZHAO ³ ; Jinlong ZHANG ¹ ; Hong QIN ¹ ; Miaomiao WANG ¹ ; Yao SU ¹ ; Minzhu TANG ³ ; Lei HAN ⁴ ; Na SUN ¹
Author Information

1. Department of Occupational Health, Center for Disease Control and Prevention of Wuxi.
2. Department of Quality Management, Center for Disease Control and Prevention of Wuxi.
3. Department of respiratory medicine, Wuxi Eighth People's Hospital.
4. Institute of Occupational Disease Prevention, Jiangsu Provincial Center for Disease Prevention and Control.
Publication Type:Journal Article
Keywords: ADGRG3; Biomarker; Silicosis; lncRNA; rs1814521
MeSH: Case-Control Studies; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Polymorphism, Single Nucleotide; RNA, Long Noncoding/genetics*; Silicosis/genetics*
From:Environmental Health and Preventive Medicine 2022;27(0):5-5
CountryJapan
Language:English
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.