Antibody dependent cell mediated cytotoxicity (ADCC) has shown to be associated with slower disease progression in Human Immunodeficiency Virus (HIV) infection [
1‐
5]. The RV144 HIV vaccine trial has shown the correlation between lower infection rates and higher ADCC responses among vaccine recipients [
6], highlighting the importance of ADCC responses in HIV protection. The ADCC is mediated primarily by natural killer (NK) cells through binding of the FcγRIIIa (CD16a) receptor with the Fc portion of the antibodies bound to the specific antigen expressed on the target cells. This binding initiates secretion of granzyme and perforin by NK cells resulting in the lysis of the target cell [
7]. Thus, for strong ADCC responses; binding affinity of FcγRIIIa receptor and the Fc portion of the antibody is important [
8,
9] and the polymorphic changes in this receptor are likely to affect the binding affinity of the FcγRIIIa receptor which might influence the ADCC activity [
10‐
12]. Single nucleotide polymorphism (SNP) of Fc receptor gene of FcγRIIIa - V158F or V176F is known to result in low functioning receptor with phenylalanine (F) and high functioning receptor with valine (V) [
13,
14]. Populations like Dutch, [
15] Sami, Norwegian, [
16] Japanese, [
14] African American, [
12] British, and northern Indian [
17] have shown this polymorphism at 158 amino acid position while Asian Indian [
13], Malaysian [
5], Chinese [
18], Korean [
19], Thais [
20] etc. have shown this polymorphism at 176 position. The V158F polymorphism was found to be associated with augmented ADCC response to rituximab, an anti-cancer monoclonal therapeutic antibody in in-vitro experiments, suggesting that the individuals expressing at least one valine at amino acid position 158 in FcγRIIIa might show better rituximab-mediated ADCC [
14,
21]. This polymorphism is in the exon 4 and is reported to alter the protein confirmation and thus influences binding affinity of FcγRIIIa and Fc region of antibodies involved in ADCC [
14,
21]. However, no information is available about this polymorphism in HIV infection and about its influence on the HIV-specific ADCC responses. Therefore in the present study, the presence of polymorphism in FcγRIIIa receptor was assessed by sequencing the exon 4 of FcγRIIIa receptor and the association of this polymorphism with the HIV-specific ADCC responses was determined. Our study population showed F to V transition at 176 amino acid position when the sequences were compared with the reference sequence from UCSC browser. Additionally, another polymorphism was observed at amino acid position 158, resulting in a substitution of tyrosine to histidine (Y158H). Both the polymorphisms observed to influence HIV-specific ADCC activity. Additionally Y158H has shown possibility of association with HIV acquisition.