PCK1 as a potential hub gene in distinguishing lactate metabolism between rheumatoid arthritis and osteoarthritis.

Background: Lactate is notably involved in the advancement of rheumatoid arthritis (RA) and osteoarthritis (OA). Nevertheless, the causal association between these conditions and lactate remains uncertain. This study aims to use Mendelian randomization (MR) to investigate their relationship with lactate and understand the genetic differences in lactate metabolism between them. Methods: Genetic data for RA, OA, and lactate metabolism were obtained from GWAS, GEO, and MSigDB databases. MR analysis was performed using the inverse variance weighted (IVW) method. Differential gene expression analysis was conducted using the "limma" package, and Gene Set Enrichment Analysis (GSEA) was performed with GSEA software. Immune cell infiltration was assessed using the CIBERSORT platform. Validation of differentially expressed genes was carried out Results: MR analysis indicated a causal relationship between RA and OA with lactate levels. Differential gene expression analysis revealed that PCK1 is a key gene underlying the metabolic differences in lactate levels between RA and OA. Conclusion: This study provides genetic evidence supporting the causal relationship between RA, OA, and lactate levels. Additionally, PCK1 is identified as a pivotal target implicated in the metabolic disparities of lactate between RA and OA, highlighting its potential significance in RA therapeutics.