This study identified and replicated a promising novel association between rs4878712, located in the FRMPD1 gene, and HIV acquisition. FRMPD1 has not been previously associated with HIV and its function is unclear, though it may play a role in subcellular location of activator of G-protein signaling 3 (AGS3)[44] and interact with Leu-Gly-Asn repeat-enriched protein (LGN).[45] Analysis of gene expression data revealed that rs4878712 is an exon-level eQTL for the FBXO10 gene and that FBXO10 expression is inversely associated with BCL2 expression: the HIV-protective G allele reducing FBXO10 expression, and reduced FBXO10 expression being associated with increased expression of BCL2 in healthy lymphoblastoid cells. FBXO10 is part of an SCF E3 ubiquitin ligase that targets Bcl-2 protein for degradation[40] and higher basal level of Bcl-2 protein is linked to reduced viral replication and infectivity of HIV in the acute phase, potentially distinguishing those who will have an acute infection and those who will develop a persistent one.[42] We hypothesize that Bcl-2 upregulation may be assisted by the putative effect of the rs4878712-G allele on reducing FBXO10 expression, providing less SCF E3
