From Gene Discovery to Stroke Risk: C5orf24's Pivotal Role Uncovered

Stroke is a leading cause of death and disability worldwide. It is crucial to understand the influencing factors and potential mechanisms of stroke, as well as reducing its risk. This study identified the expression of the B230219D22Rik gene in mouse microglial cells, corresponding to the human gene C5orf24, using the NCBI database. We then validated the role of C5orf24 in stroke using quantitative real-time PCR, enzyme-linked immunosorbent assay, western blot and Mendelian randomization (MR) analysis. Additionally, we evaluated the causal association of C5orf24 with three other vascular diseases: coronary heart disease, myocardial infarction, and embolism. The gene B230219D22Rik and C5orf24 expressed in microglia was observed to have reduced expression in mouse and human cell stroke models, respectively. In MR analysis, we found a significant causal relationship between increased C5orf24 levels and reduced stroke risk (OR = 0.68, 95% CI 0.48-0.98, P = 4.07 × 10^-2). However, this association was not observed in three other vascular diseases. To further explore the function of C5orf24 in stroke, we overexpressed C5orf24 in the oxygen-glucose deprivation/reperfusion (OGD/R) model of human microglial cell line clone 3 (HMC3) in vitro and found that C5orf24 inhibited the expression of inflammatory factors IL-1β and IL-6. In our study, we revealed a causal relationship between elevated levels of C5orf24 and a reduced risk of stroke through cell experiments and MR analysis, and found that inflammation might play a mediating role. This suggests that C5orf24 could be a promising drug target for stroke treatment.