Rheumatoid arthritis and gliostatin: a two-sample Mendelian randomization analysis and RT-PCR validation

Background: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease of unknown etiology. Cuproptosis, a novel form of cell death, is characterized by cytotoxicity originating from copper ions. To date, the relationship between cuproptosis-related gene gliostatin (GLS) and RA.

Methods: All raw data were retrieved from the Gene Expression Omnibus (GEO) public database. The expression level of genes between RA and healthy samples was evaluated to identify differentially expressed genes. Then, LASSO regression was used to screen disease signature genes, and a nomogram was constructed based on five hub genes to predict disease scores. Validation experiments were performed using quantitative real-time PCR (qRT-PCR) to detect the most significant CRGs. Finally, the causal relationship between GLS and RA was analyzed through Mendelian randomization methodology.

Results: Five differentially expressed CRGs (NLRP3, ATP7A, MTF1, GLS, and DBT) were identified between normal and RA samples, all of which were validated as disease-specific genes through LASSO regression analysis. Meanwhile, the nomogram demonstrated a positive correlation between RA and the expression of GLS. Furthermore, q-PCR revealed that the expression level of GLS was higher in RA patients compared to those in the control group. Taken together, a causal relationship between GLS and RA was corroborated through Mendelian randomization.

Conclusion: GLS, a cuproptosis-related gene, is closely associated with RA and plays a significant role in its diagnosis. Key Points • The causal relationship between GLS and RA is proved by Mendelian randomization.