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 < .05, using HCs), whereas KIR3DS1 may associate with a reduced risk (p < .001, using HCs). In the subgroup analyses, among Africans, KIR2DS4 also revealed a significant risk of HIV-1 infection (p < .05), whereas KIR2DL2, 2DL5, and 2DS3 conferred a protective role (p < .05). KIR2DL2 and 3DL1 showed an increased risk of acquiring infection among Caucasians (p < .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 < .05). Moreover, among Chinese, KIR2DL3 was significantly lower in frequency in TPs when compared with LTNPs (p < .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 emphasizes that this outcome differs according to specific populations.
Keywords: HIV-1; disease progression; killer immunoglobulin-like receptor genes; meta-analysis; population genetics; susceptibility.