Zhao Rui, Tao Xiaobo, Zhang Wendi, Li Siqi, Zhou Shenxuan, Ning Anhui, Li Zhenyu, Chu Minjie, Wang Wei, Jiang Junhong
Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou 215006, China; Department of Respiratory, Wuxi Eighth People's Hospital, Wuxi 214000, China.
Department of Epidemiology, School of Public Health, Nantong University, Nantong, Jiangsu, China.
Ecotoxicol Environ Saf. 2025 Jan 1;289:117679. doi: 10.1016/j.ecoenv.2025.117679. Epub 2025 Jan 10.
Identifying the common functional single-nucleotide polymorphisms (SNPs) that can both affect the susceptibility to idiopathic pulmonary fibrosis (IPF) and silicosis.
We first integrated the genome-wide association studies (GWASs) of IPF and silicosis to obtain the shared SNPs. Following this, functional expression quantitative trait locus (eQTL)-SNPs were identified by the GTEx database. This was followed by the validation of the correlation between these eQTL-SNPs and silicosis susceptibility through an additional case-control study including 194 silicosis cases and 235 healthy controls.
A total of 10 eQTL-SNPs that may affect silicosis susceptibility (P < 0.05) were obtained after the integration of the GWASs of IPF and silicosis, and a series of rigorous selection principles. Subsequently, the results of integrating the validation stage and the screening stage indicated that the variant T allele of rs1620530 located in the MAD1L1 (additive model: OR= 1.56, 95 % CI = 1.21-2.01, P = 0.001) and the variant G allele of rs2070063 located in the SERTAD2 (additive model: OR= 1.60, 95 % CI = 1.24-2.06, P < 0.001) were associated with increased silicosis susceptibility. The joint analysis indicated the risk of developing silicosis was higher in individuals who carried more unfavorable alleles of rs1620530 and rs2070063.
The rs1620530 and rs2070063 may affect the silicosis susceptibility by regulating the expression of the MAD1L1 and SERTAD2, respectively. Further biological experiments are warranted to elucidate the underlying biological mechanisms between these two SNPs and the increased susceptibility to silicosis.
鉴定既能影响特发性肺纤维化（IPF）易感性又能影响矽肺易感性的常见功能性单核苷酸多态性（SNP）。
我们首先整合IPF和矽肺的全基因组关联研究（GWAS）以获得共享的SNP。在此之后，通过GTEx数据库鉴定功能性表达数量性状位点（eQTL）-SNP。随后，通过一项纳入194例矽肺病例和235例健康对照的额外病例对照研究，验证这些eQTL-SNP与矽肺易感性之间的相关性。
整合IPF和矽肺的GWAS以及一系列严格的筛选原则后，共获得10个可能影响矽肺易感性的eQTL-SNP（P<0.05）。随后，整合验证阶段和筛选阶段的结果表明，位于MAD1L1的rs1620530的变异T等位基因（加性模型：OR = 1.56，95%CI = 1.21 - 2.01，P = 0.001）和位于SERTAD2的rs2070063的变异G等位基因（加性模型：OR = 1.60，95%CI = 1.24 - 2.06，P<0.001）与矽肺易感性增加相关。联合分析表明，携带rs1620530和rs2070063更多不利等位基因的个体患矽肺的风险更高。
rs1620530和rs2070063可能分别通过调节MAD1L1和SERTAD2的表达来影响矽肺易感性。有必要进行进一步的生物学实验以阐明这两个SNP与矽肺易感性增加之间的潜在生物学机制。
