DISSyphilis and the risk of HIV infection: A Mendelian randomization study

Objection: To assess the causal effect of syphilis on HIV infection by Mendelian randomization analysis. Methods: The data of syphilis and HIV infection were obtained from genome-wide association studies, Mendelian randomization analyses were conducted using methods such as weighted median, MR Egger, and inverse variance to evaluate the causal relationship between syphilis and HIV infection. Gene expression data of persons living with HIV (PLWH) and single-cell RNA sequencing profiles were obtained from the GEO database. Analysis involved the identification of key molecules and relevant signaling pathways. Results: MR analysis showed a significant causal relationship between syphilis and HIV infection (WM, OR: 1.098, 95%CI: 1.033-1.217, P = 0.003; IVW, OR: 1.095, 95%CI: 1.048-1.145, P < 0.001). We discovered that rs138697742, a genetic variant related to the RPAIN gene, is associated with HIV infection, and influences the expression of RPAIN, possibly contributing to the progression of the disease. Moreover, single-cell data analysis revealed the cellular communication patterns within PLWH, with monocytes appearing to play a crucial role. Conclusion: In summary, our study reveals a direct causal relationship between syphilis and HIV infection. Additionally, the upregulation of RPAIN gene expression resulting from genetic mutations may serve as a key factor in promoting the progression of HIV infection. Targeting the RPAIN/GALECTIN merges as a promising novel therapeutic target for managing HIV infection.