title: FCGR2C Polymorphisms Associated with HIV-1 Vaccine Protection Are Linked to Altered Gene Expression of Fc-γ Receptors in Human B Cells.
abstract: 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.
authors.affiliation: Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington, United States of America.
authors.forename: Xinxia
authors.initials: X
authors.lastname: Peng
authors.affiliation: Department of Biostatistics, Bioinformatics, and Epidemiology, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Shuying S
authors.initials: SS
authors.lastname: Li
authors.affiliation: Department of Biostatistics, Bioinformatics, and Epidemiology, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Gilbert
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Geraghty
authors.affiliation: Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington, United States of America.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Katze
mesh_terms: D016915:AIDS Vaccines / Q000627:therapeutic use*; D000483:Alleles; D017398:Alternative Splicing; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism* / Q000821:virology*; D005060:Europe; D017353:Gene Deletion; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000235:genetics* / Q000517:prevention & control*; D015497:HIV-1; D006720:Homozygote; D006801:Humans; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D011961:Receptors, Fc; D017452:Receptors, IgG / Q000096:biosynthesis* / Q000235:genetics*; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D017423:Sequence Analysis, RNA
chemical_list: D016915:AIDS Vaccines; C445323:FCGR2A protein, human; C000609718:FCGR2C protein, human; C452186:FCRLA protein, human; D011961:Receptors, Fc; D017452:Receptors, IgG; D011971:Receptors, Immunologic