Open AccessEffects of the killer immunoglobulin–like receptor (KIR) polymorphisms on HIV acquisition: A meta-analysis
Author(s) -
Suwit Chaisri,
Noel Pabalan,
Sompong Tabunhan,
Phuntila Tharabenjasin,
Nipaporn Sankuntaw,
Chanvit Leelayuwat
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0225151
Subject(s) - antibody , human immunodeficiency virus (hiv) , biology , meta analysis , immunoglobulin g , receptor , virology , immunology , genetics , medicine
Background Genetic 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. Methods A 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. Results We 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 (P c ). These protective effects pointed to the Caucasian subgroup in 2DL3 (OR 0.19, 95% CI 0.09, 0.40, P c < 10 −3 ) and 3DS1S1 (OR 0.37, 95% CI 0.24, 0.56, P c < 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 (P c interaction < 10 −4 ). Conclusion Multiple 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.