Combining epigenomic and genomic analyses with functional experimentation, researchers from Xi'an Jiaotong University have uncovered a potential new therapeutic target for rheumatoid arthritis (RA). Genome-wide association studies have associated multiple SNPs at chromosome 2p14 with RA, but their functional roles in the disease's pathology is unknown. Hypothesizing that intronic SNPs at 2p14 might act as regulatory elements that affect gene expression in fibroblast-like synoviocytes (FLS) — synovial tissue cells that help drive RA onset and progression — the researchers performed bioinformatic analyses using epigenomic annotation, high-throughput chromatin interaction, and other data, followed by functional validation experiments. As reported in this week's American Journal of Human Genetics, they show that intronic RA SNPs affect enhancer activity to directly regulate the expression of a gene, SPRED2, that is involved in inflammation. They further show that SPRED2 works with another gene to protect against RA by inhibiting the migration and invasion of rheumatoid FLSs. "Our findings decipher the molecular mechanisms behind the GWAS signals at 2p14 for RA and emphasize SPRED2 as a potential candidate gene for RA, providing a potential target and direction for precise treatment of RA," the study's authors write.
Potential New Therapeutic Target for Rheumatoid Arthritis Discovered
Mar 16, 2023