Effects of the killer immunoglobulin–like receptor (KIR) polymorphisms on HIV acquisition: A meta-analysis

Abstract

BackgroundGenetic involvement of Killer Immunoglobulin-like Receptor (KIR) polymorphisms and Human Immunodeficiency Virus (HIV)-exposed seronegative (HESN) compared to HIV-infected (HIVI) individuals has been reported. However, inconsistency of the outcomes reduces precision of the estimates. A meta-analysis was applied to obtain more precise estimates of association.MethodsA multi-database literature search yielded thirteen case-control studies. Risks were expressed as odds ratios (ORs) and 95% confidence intervals (CIs) with significance set at a two-tailed P-value of ≤ 0.05. We used two levels of analyses: (1) gene content that included 13 KIR polymorphisms (2DL1-3, 2DL5A, 2DL5B, 2DS1-3, 2DS4F, 2DS4D, 2DS5, 3DL1 and 3DS1); and (2) 3DL1/S1 genotypes. Subgroup analysis was ethnicity-based (Caucasians, Asians and Africans). Outlier treatment was applied to heterogeneous effects which dichotomized the outcomes into pre-outlier (PRO) and post-outlier (PSO). Multiple comparisons were addressed with the Bonferroni correction.ResultsWe generated 52 and 18 comparisons from gene content and genotype analyses, respectively. Of the 70 comparisons, 13 yielded significant outcomes, two (indicating reduced risk) of which survived the Bonferroni correction (Pc). These protective effects pointed to the Caucasian subgroup in 2DL3 (OR 0.19, 95% CI 0.09, 0.40, Pc < 10−3) and 3DS1S1 (OR 0.37, 95% CI 0.24, 0.56, Pc < 10−3). These two PSO outcomes yielded effects of increased magnitude and precision, as well as raised significance and deemed robust by sensitivity analysis. Of the two, the 2DL3 effect was improved with a test of interaction (Pc interaction < 10−4).ConclusionMultiple meta-analytical treatments presented strong evidence of the protective effect (up to 81%) of the KIR polymorphisms (2DL3 and 3DS1S1) among Caucasians. The Asian and African outcomes were inconclusive due to the low number of studies.

Relationship between KIR genotypes and HLA-ligands with SARS-CoV-2 infection in the Saudi population

“…The involvement of Killer Immunoglobulin-like Receptor (KIR) polymorphisms and the Human Immune response against viral infection has been reported by a significant number of researchers ( Wang et al, 2018 , Chaisri et al, 2019 , van Erp et al, 2019 ).…”

Expression of Killer Immunoglobulin Receptor Genes among HIV-Infected Individuals with Non-AIDS Comorbidities

“…Moreover, we were unable to investigate the interaction between KIRs and their putative human leukocyte antigen class I (HLA-I) ligand. The latter has been implicated in controlling HIV-disease progression [ 75 – 79 ] and in the control or the progression of other viral diseases including human influenza virus, viral hepatitis (HCV and HBV), and human cytomegalovirus (HCMV) [ 26 , 77 ].…”

Killer cell immunoglobulin‐like receptor three domains long cytoplasmic tail 1 gene *007 may modulate disease progression of human immunodeficiency virus‐1 infection in the Japanese population

“…A GWAS study in British hemophiliac patients concluded that there was no significant association between HLA/KIR genotypes and resistance to HIV‐1 infection, so that any specific combinations of KIR alleles and HLA alleles might not be involved in the resistance to HIV‐1 infection (Vince et al., 2014), although other reports indicated a significant association of specific HLA alleles or specific HLA/KIR combinations in other hemophiliac cohorts (Gao et al., 2010; Tang et al., 2008). In a meta‐analysis of KIR polymorphisms and HIV‐1 relationship, KIR2DL3 and KIR3DS1 showed a significant association only in Europeans, while the association in Asians was inconclusive due to insufficient studied numbers (Chaisri et al., 2019). In addition, it was pointed out that it is not easy to obtain the expected effect by the GWAS analysis due to the complexity of the configuration of KIR gene polymorphisms.…”