The observed reduced expression of FBXO10 associated with the G allele of rs4878712 may have biological links to risk of HIV acquisition. FBXO10 is a component of a Skp1-Cul1-F-box protein (SCF) E3 ubiquitin ligase complex that directly targets Bcl-2 protein for degradation.[40] There is interplay between Bcl-2 and HIV in a number of ways over the course of infection,[41] but in the acute phase, higher levels of Bcl-2 are protective in vitro and in animal models.[42,43] Thus, lower levels of FBXO10 expression could be expected to lead to less tagging of Bcl-2 protein for degradation, higher levels of Bcl-2, and greater protection against HIV. Consistent with this possibility, we observed an inverse association between expression of FBXO10 and BCL2 (r = -0.49, P = 8 x10-5; Fig. 3).
