关键词: 系统性红斑狼疮, FAM167A-BLK基因座, SNP, 增强子

Abstract: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with multi-organ involvement. The FAM167A-BLK locus at 8p23 has been identified as a genetic susceptibility locus for SLE by previous genome-wide association studies (GWAS). To explore the role of functional single-nucleotide polymorphisms (SNPs) within this locus on the regulation of BLK and FAM167A genes, we perform comprehensive functional annotation using GCTA and fnGWAS approaches to identify candidate functional SNPs，and verify them through dual-luciferase reporter assays, shRNA knockdown experiments, and CRISPR/dCas9 knockdown experiments. The results show that four functional SNPs exhibit allele-specific enhancing effect on BLK expression, while showing no discernible regulatory influence on FAM167A expression. Importantly, BLK is shown to regulate the expression of FAM167A. These findings highlight FAM167A as a potential pathogenic gene contributing to SLE. This study expands the mechanistic understanding of genetic regulation at the FAM167A-BLK locus and provides new insights into SLE development.

Key words: SLE, FAM167A-BLK locus, SNP, enhancer