The SNP rs4878712 could be linked with HIV in at least two other ways. First, a recent study of FBXO10 as a potential oncogene found that manipulation of Lens epithelium-derived growth factor/p75 (LEDGF/p75) protein was positively correlated with FBXO10 expression in a cellular oxidase stress model. LEDGF/p75 is a key co-factor tethering HIV DNA to host DNA and directing viral DNA integration.[46] Depletion or knockdown of LEDGF/p75 substantially reduces infectivity of the virus.[47] If lower FBXO10 expression reduces available LEDGF/p75, then it may contribute to protection from HIV infection. Second, ENCODE data identifies rs4878712 as modifying the regulatory motif PRDM1_disc1, suggesting that rs4878712 may alter the transcription binding site for PRDI-BF1 on the FRMPD1 gene. Of note, the PRDI-BF1 (or BLIMP-1) protein is a transcriptional repressor broadly implicated in T-cell inhibition during HIV infection.[48]
