217 HIV Infection Risk Association with FCG Receptor Polymorphism

Abstract

Antibody-dependent cellular cytotoxicity (ADCC) is a mechanism for HIV-specific antibodies to target infected cells for destruction by cytotoxic effectors. The Fc portion of IgG antibodies bind cytotoxic effector cells through a family of Fc receptors that include FCGR3A (CD16). Alternately, antibody binding to Fc receptor delivers an activating signal to the effector cells. Thus there is a balance between effector cell stimulation and target cell killing during ADCC. Single nucleotide polymorphisms (SNP) in the Fc receptor gene FCGR3A alter the amino acid sequence and encode high or low functioning proteins. We predicted that elite controller groups (HIV+ individuals with durable viurus suppression without taking antiretroviral drugs) would have increased frequencies of the high functioning allelels, compared to HIV progressors or uninfected controls. Genomic DNA was analyzed from individuals with no HIV infection, Elite controllers and HIV progressors on HAART for a known polymorphism in the FCGR3A gene that has functional relevance to ADCC function. The rs396991 polymorphism results in a T (F amino acid) or a G (V amino acid) allele at the SNP position. PCR was used to amplify a region of FCGR3A and an analysis of rs396691 was done using the ABISnapshot multiplex kit. An allele frequency of T (0.82) and G (0.18) for normal donors, T (0.75) and G (0.25) for elite controllers and T (0.58) and G (0.42) for HIV progressors. These results of higher frequencies of high functioning alleles in HIV progressors suggest that this allele may be responsible for chronic lymphocyte activation that is a feature of progressing HIV disease.