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Influence of single-nucleotide polymorphisms in TLR3 (rs3775291) and TLR9 (rs352139) on the risk of CMV infection in kidney transplant recipients

Risk stratification for cytomegalovirus (CMV) infection after kidney transplantation (KT) remains to be determined. Since endosomal toll-like receptors (TLRs) are involved in viral sensing, we investigated the impact of common single-nucleotide polymorphisms (SNPs) located within TLR3 and TLR9 genes...

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Autores principales: Redondo, Natalia, Rodríguez-Goncer, Isabel, Parra, Patricia, Ruiz-Merlo, Tamara, López-Medrano, Francisco, González, Esther, Polanco, Natalia, Trujillo, Hernando, Hernández, Ana, San Juan, Rafael, Andrés, Amado, Aguado, José María, Fernández-Ruiz, Mario
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9374175/
https://www.ncbi.nlm.nih.gov/pubmed/35967300
http://dx.doi.org/10.3389/fimmu.2022.929995
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author Redondo, Natalia
Rodríguez-Goncer, Isabel
Parra, Patricia
Ruiz-Merlo, Tamara
López-Medrano, Francisco
González, Esther
Polanco, Natalia
Trujillo, Hernando
Hernández, Ana
San Juan, Rafael
Andrés, Amado
Aguado, José María
Fernández-Ruiz, Mario
author_facet Redondo, Natalia
Rodríguez-Goncer, Isabel
Parra, Patricia
Ruiz-Merlo, Tamara
López-Medrano, Francisco
González, Esther
Polanco, Natalia
Trujillo, Hernando
Hernández, Ana
San Juan, Rafael
Andrés, Amado
Aguado, José María
Fernández-Ruiz, Mario
author_sort Redondo, Natalia
collection PubMed
description Risk stratification for cytomegalovirus (CMV) infection after kidney transplantation (KT) remains to be determined. Since endosomal toll-like receptors (TLRs) are involved in viral sensing, we investigated the impact of common single-nucleotide polymorphisms (SNPs) located within TLR3 and TLR9 genes on the occurrence of overall and high-level (≥1,000 IU/ml) CMV infection in a cohort of 197 KT recipients. Homozygous carriers of the minor allele of TLR3 (rs3775291) had higher infection-free survival compared with reference allele carriers (60.0% for TT versus 42.3% for CC/CT genotypes; P-value = 0.050). Decreased infection-free survival was observed with the minor allele of TLR9 (rs352139) (38.2% for TC/CC versus 59.3% for TT genotypes; P-value = 0.004). After multivariable adjustment, the recessive protective effect of the TLR3 (rs3775291) TT genotype was confirmed (adjusted hazard ratio [aHR]: 0.327; 95% CI: 0.167–0.642; P-value = 0.001), as was the dominant risk-conferring effect of TLR9 (rs352139) TC/CC genotypes (aHR: 1.865; 95% CI: 1.170–2.972; P-value = 0.009). Carriers of the TLR9 (rs352139) TC/CC genotypes showed lower CMV-specific interferon-γ-producing CD4+ T-cell counts measured by intracellular cytokine staining compared with the TT genotype (median of 0.2 versus 0.7 cells/μl; P-value = 0.003). In conclusion, TLR3/TLR9 genotyping may inform CMV infection risk after KT.
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spelling pubmed-93741752022-08-13 Influence of single-nucleotide polymorphisms in TLR3 (rs3775291) and TLR9 (rs352139) on the risk of CMV infection in kidney transplant recipients Redondo, Natalia Rodríguez-Goncer, Isabel Parra, Patricia Ruiz-Merlo, Tamara López-Medrano, Francisco González, Esther Polanco, Natalia Trujillo, Hernando Hernández, Ana San Juan, Rafael Andrés, Amado Aguado, José María Fernández-Ruiz, Mario Front Immunol Immunology Risk stratification for cytomegalovirus (CMV) infection after kidney transplantation (KT) remains to be determined. Since endosomal toll-like receptors (TLRs) are involved in viral sensing, we investigated the impact of common single-nucleotide polymorphisms (SNPs) located within TLR3 and TLR9 genes on the occurrence of overall and high-level (≥1,000 IU/ml) CMV infection in a cohort of 197 KT recipients. Homozygous carriers of the minor allele of TLR3 (rs3775291) had higher infection-free survival compared with reference allele carriers (60.0% for TT versus 42.3% for CC/CT genotypes; P-value = 0.050). Decreased infection-free survival was observed with the minor allele of TLR9 (rs352139) (38.2% for TC/CC versus 59.3% for TT genotypes; P-value = 0.004). After multivariable adjustment, the recessive protective effect of the TLR3 (rs3775291) TT genotype was confirmed (adjusted hazard ratio [aHR]: 0.327; 95% CI: 0.167–0.642; P-value = 0.001), as was the dominant risk-conferring effect of TLR9 (rs352139) TC/CC genotypes (aHR: 1.865; 95% CI: 1.170–2.972; P-value = 0.009). Carriers of the TLR9 (rs352139) TC/CC genotypes showed lower CMV-specific interferon-γ-producing CD4+ T-cell counts measured by intracellular cytokine staining compared with the TT genotype (median of 0.2 versus 0.7 cells/μl; P-value = 0.003). In conclusion, TLR3/TLR9 genotyping may inform CMV infection risk after KT. Frontiers Media S.A. 2022-07-29 /pmc/articles/PMC9374175/ /pubmed/35967300 http://dx.doi.org/10.3389/fimmu.2022.929995 Text en Copyright © 2022 Redondo, Rodríguez-Goncer, Parra, Ruiz-Merlo, López-Medrano, González, Polanco, Trujillo, Hernández, San Juan, Andrés, Aguado and Fernández-Ruiz https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Redondo, Natalia
Rodríguez-Goncer, Isabel
Parra, Patricia
Ruiz-Merlo, Tamara
López-Medrano, Francisco
González, Esther
Polanco, Natalia
Trujillo, Hernando
Hernández, Ana
San Juan, Rafael
Andrés, Amado
Aguado, José María
Fernández-Ruiz, Mario
Influence of single-nucleotide polymorphisms in TLR3 (rs3775291) and TLR9 (rs352139) on the risk of CMV infection in kidney transplant recipients
title Influence of single-nucleotide polymorphisms in TLR3 (rs3775291) and TLR9 (rs352139) on the risk of CMV infection in kidney transplant recipients
title_full Influence of single-nucleotide polymorphisms in TLR3 (rs3775291) and TLR9 (rs352139) on the risk of CMV infection in kidney transplant recipients
title_fullStr Influence of single-nucleotide polymorphisms in TLR3 (rs3775291) and TLR9 (rs352139) on the risk of CMV infection in kidney transplant recipients
title_full_unstemmed Influence of single-nucleotide polymorphisms in TLR3 (rs3775291) and TLR9 (rs352139) on the risk of CMV infection in kidney transplant recipients
title_short Influence of single-nucleotide polymorphisms in TLR3 (rs3775291) and TLR9 (rs352139) on the risk of CMV infection in kidney transplant recipients
title_sort influence of single-nucleotide polymorphisms in tlr3 (rs3775291) and tlr9 (rs352139) on the risk of cmv infection in kidney transplant recipients
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9374175/
https://www.ncbi.nlm.nih.gov/pubmed/35967300
http://dx.doi.org/10.3389/fimmu.2022.929995
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