FCGR genetics in HIV disease (88.21)

Abstract

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 binds cytotoxic effector cells through a family of Fc receptors that include FCGR3A (CD16). Antibody binding to Fc receptor also 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 HIV elite controller groups would have increased frequencies of the high functioning allele 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 polymorphism rs396991, that 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 rs396991 was done using the ABISnapshot multiplex kit. An allele frequency of T/G 0.82/0.18 for normal donors, T/G 0.75/0.25 for elite controllers and T/G 0.58/0.42 for HIV progressors was found. 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.