To explore the host genetic factors influencing the visceral leishmaniasis relapse in India by NGS exome analysis

Single nucleotide variants in VL relapse patients compared to non relapse highlight key genes impacting immune pathways. EP300, essential for chromatin remodeling, was found in all 14 relapse patients, indicating its strong association with VL relapse. MRS2 mutations, affecting immune signaling were present in 10 relapse patients but absent in non-relapse suggesting a role in relapse pathogenesis. Similarly ATF7IP2 variants were found in 8 relapse patients, potentially influencing relapse. GOLGA8K and SCL37A2 mutations linked to immunodeficiencies were prevalent in over 90 percent of relapse patients implicating their role in relapse development. HERC5 alterations regulating cytokine production were found in 12 out of 14 relapse patients. While other variants lacked direct immune pathway associations they could influence VL recurrence. PPI network analysis highlighted EP300s central role, though further evidence is needed. Forest plot analysis identified 11 variants potentially protective against VL relapse including KIR2DL3 NOX5 and PLA2R1 known for their immunological functions.