The Role of Killer Immunoglobulin-like Receptor (KIR) Genes in Susceptibility to HIV-1 Infection and Disease Progression: A Meta-analysis.

Genetic studies on the association of the killer immunoglobulin-like receptor (KIR) genes with HIV-1 infection and disease progression have been widely carried out with somewhat contradictory results. Therefore, we undertook a quantitative assessment based on 25 studies [involving 3,216 HIV-1 infected subjects, 1,690 exposed uninfected subjects, 1,262 healthy controls (HCs), 748 typical progressors (TPs), and 244 long-term nonprogressors (LTNPs)] to further define the roles of KIR in HIV-1 control/susceptibility. An overall analysis, showed that, among the 16 KIR genes, the presence of KIR2DS4 may associate with an elevated risk of HIV-1 infection (P < 0.05, using HCs), while KIR3DS1 may associate with a reduced risk (P < 0.001, using HCs). In the subgroup analyses, among Africans, KIR2DS4 also revealed a significant risk of HIV-1 infection (P < 0.05), while KIR2DL2, 2DL5, and 2DS3 conferred a protective role (P < 0.05). KIR2DL2 and 3DL1 showed an increased risk of acquiring infection among Caucasians (P < 0.05). A negative effect on susceptibility to infection for KIR2DL1, 2DL3 and 3DS1 was found among East Asians. 3DS1 conferred a protective effect of HIV-1 infection among serodiscordant couples (P < 0.05). Moreover, among Chinese, KIR2DL3 was significantly lower in frequency in TPs when compared to LTNPs (P < 0.05), indicating a possible role in the delay of disease progression. This meta-analysis supports the individual studies that associate specific KIR genes with HIV-1 infection and disease progression and further emphasises that this outcome differs according to specific populations.