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

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 me...

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Autores principales: Chaisri, Suwit, Pabalan, Noel, Tabunhan, Sompong, Tharabenjasin, Phuntila, Sankuntaw, Nipaporn, Leelayuwat, Chanvit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6886768/
https://www.ncbi.nlm.nih.gov/pubmed/31790432
http://dx.doi.org/10.1371/journal.pone.0225151
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author Chaisri, Suwit
Pabalan, Noel
Tabunhan, Sompong
Tharabenjasin, Phuntila
Sankuntaw, Nipaporn
Leelayuwat, Chanvit
author_facet Chaisri, Suwit
Pabalan, Noel
Tabunhan, Sompong
Tharabenjasin, Phuntila
Sankuntaw, Nipaporn
Leelayuwat, Chanvit
author_sort Chaisri, Suwit
collection PubMed
description 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.
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spelling pubmed-68867682019-12-13 Effects of the killer immunoglobulin–like receptor (KIR) polymorphisms on HIV acquisition: A meta-analysis Chaisri, Suwit Pabalan, Noel Tabunhan, Sompong Tharabenjasin, Phuntila Sankuntaw, Nipaporn Leelayuwat, Chanvit PLoS One Research Article 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. Public Library of Science 2019-12-02 /pmc/articles/PMC6886768/ /pubmed/31790432 http://dx.doi.org/10.1371/journal.pone.0225151 Text en © 2019 Chaisri et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Chaisri, Suwit
Pabalan, Noel
Tabunhan, Sompong
Tharabenjasin, Phuntila
Sankuntaw, Nipaporn
Leelayuwat, Chanvit
Effects of the killer immunoglobulin–like receptor (KIR) polymorphisms on HIV acquisition: A meta-analysis
title Effects of the killer immunoglobulin–like receptor (KIR) polymorphisms on HIV acquisition: A meta-analysis
title_full Effects of the killer immunoglobulin–like receptor (KIR) polymorphisms on HIV acquisition: A meta-analysis
title_fullStr Effects of the killer immunoglobulin–like receptor (KIR) polymorphisms on HIV acquisition: A meta-analysis
title_full_unstemmed Effects of the killer immunoglobulin–like receptor (KIR) polymorphisms on HIV acquisition: A meta-analysis
title_short Effects of the killer immunoglobulin–like receptor (KIR) polymorphisms on HIV acquisition: A meta-analysis
title_sort effects of the killer immunoglobulin–like receptor (kir) polymorphisms on hiv acquisition: a meta-analysis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6886768/
https://www.ncbi.nlm.nih.gov/pubmed/31790432
http://dx.doi.org/10.1371/journal.pone.0225151
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