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The phase III Thai RV144 vaccine trial showed an estimated vaccine efficacy (VE) to prevent HIV-1 infection of 31.2%, which has motivated the search for immune correlates of vaccine protection. In a recent report, several single nucleotide polymorphisms (SNPs) in  FCGR2C  were identified to associate with the level of VE in the RV144 trial. To investigate the functional significance of these SNPs, we utilized a large scale B cell RNA sequencing database of 462 individuals from the 1000 Genomes Project to examine associations between  FCGR2C  SNPs and gene expression. We found that the  FCGR2C  SNPs that associated with vaccine efficacy in RV144 also strongly associated with the expression of  FCGR2A/C  and one of them also associated with the expression of Fc receptor-like A ( FCRLA ), another Fc-γ receptor (FcγR) gene that was not examined in the previous report. These results suggest that the expression of FcγR genes is influenced by these SNPs either directly or in linkage with other causal variants. More importantly, these results motivate further investigations into the potential for a causal association of expression and alternative splicing of  FCGR2C  and other FcγR genes with the HIV-1 vaccine protection in the RV144 trial and other similar studies.

FCGR2C Polymorphisms Associated with HIV-1 Vaccine Protection Are Linked to Altered Gene Expression of Fc-γ Receptors in Human B Cells