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Polymorphisms of T helper cell cytokine-associated genes and survival of hemodialysis patients – a prospective study

BACKGROUND: Circulating pro-inflammatory cytokines were associated with increased relative mortality risk, while immune parameters reflecting improved T-cell function were predictors of survival in hemodialysis (HD) patients. We evaluated in the prospective study whether variants in T helper cell cy...

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Autores principales: Grzegorzewska, Alicja E., Świderska, Monika K., Mostowska, Adrianna, Warchoł, Wojciech, Jagodziński, Paweł P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5437603/
https://www.ncbi.nlm.nih.gov/pubmed/28525983
http://dx.doi.org/10.1186/s12882-017-0582-x
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author Grzegorzewska, Alicja E.
Świderska, Monika K.
Mostowska, Adrianna
Warchoł, Wojciech
Jagodziński, Paweł P.
author_facet Grzegorzewska, Alicja E.
Świderska, Monika K.
Mostowska, Adrianna
Warchoł, Wojciech
Jagodziński, Paweł P.
author_sort Grzegorzewska, Alicja E.
collection PubMed
description BACKGROUND: Circulating pro-inflammatory cytokines were associated with increased relative mortality risk, while immune parameters reflecting improved T-cell function were predictors of survival in hemodialysis (HD) patients. We evaluated in the prospective study whether variants in T helper cell cytokine-associated genes are determinants of mortality in HD patients. METHODS: The study was carried out in 532 prevalent HD subjects who were followed-up for 7 years. HRM analysis was used for IFNL3, IL12A, IL13, and IL4R genotyping. CCL2, IL12B, and IL18 were genotyped using PCR–RFLP analysis. Survival analyses were conducted using the Kaplan-Meier method and the Cox proportional hazard model. RESULTS: In univariate analyses, IFNL3 rs8099917 was associated with all-cause mortality in recessive model of inheritance (log-rank test P = 0.044), IL12A rs568408 - in dominant model (log-rank test P = 0.029). Minor homozygotes (the genotype GG) in IFNL3 rs8099917 showed shorter survival during the study (3.6, 1.0–7.0 years vs 4.7, 0.1–7.0 years, P = 0.009) than the major allele (T) bearers. The rs8099917 GG patients demonstrated higher risk of death than the remaining patients (GT + TT) (OR 1.94, 95%CI 1.11–3.40, P = 0.020). Major homozygosity (the genotype GG) in IL12A rs568408 was associated with higher mortality than that shown in bearers of the minor allele (AA + AG) (HR 1.31, 95%CI 1.02–1.69, P = 0.035). In multivariate analyses, however, the mentioned polymorphisms were not independent predictors of survival. CONCLUSIONS: Polymorphisms of IFNL3 rs8099917 and IL12A rs568408 contribute to survival of HD patients, but not as independent factors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12882-017-0582-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-54376032017-05-22 Polymorphisms of T helper cell cytokine-associated genes and survival of hemodialysis patients – a prospective study Grzegorzewska, Alicja E. Świderska, Monika K. Mostowska, Adrianna Warchoł, Wojciech Jagodziński, Paweł P. BMC Nephrol Research Article BACKGROUND: Circulating pro-inflammatory cytokines were associated with increased relative mortality risk, while immune parameters reflecting improved T-cell function were predictors of survival in hemodialysis (HD) patients. We evaluated in the prospective study whether variants in T helper cell cytokine-associated genes are determinants of mortality in HD patients. METHODS: The study was carried out in 532 prevalent HD subjects who were followed-up for 7 years. HRM analysis was used for IFNL3, IL12A, IL13, and IL4R genotyping. CCL2, IL12B, and IL18 were genotyped using PCR–RFLP analysis. Survival analyses were conducted using the Kaplan-Meier method and the Cox proportional hazard model. RESULTS: In univariate analyses, IFNL3 rs8099917 was associated with all-cause mortality in recessive model of inheritance (log-rank test P = 0.044), IL12A rs568408 - in dominant model (log-rank test P = 0.029). Minor homozygotes (the genotype GG) in IFNL3 rs8099917 showed shorter survival during the study (3.6, 1.0–7.0 years vs 4.7, 0.1–7.0 years, P = 0.009) than the major allele (T) bearers. The rs8099917 GG patients demonstrated higher risk of death than the remaining patients (GT + TT) (OR 1.94, 95%CI 1.11–3.40, P = 0.020). Major homozygosity (the genotype GG) in IL12A rs568408 was associated with higher mortality than that shown in bearers of the minor allele (AA + AG) (HR 1.31, 95%CI 1.02–1.69, P = 0.035). In multivariate analyses, however, the mentioned polymorphisms were not independent predictors of survival. CONCLUSIONS: Polymorphisms of IFNL3 rs8099917 and IL12A rs568408 contribute to survival of HD patients, but not as independent factors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12882-017-0582-x) contains supplementary material, which is available to authorized users. BioMed Central 2017-05-19 /pmc/articles/PMC5437603/ /pubmed/28525983 http://dx.doi.org/10.1186/s12882-017-0582-x Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Grzegorzewska, Alicja E.
Świderska, Monika K.
Mostowska, Adrianna
Warchoł, Wojciech
Jagodziński, Paweł P.
Polymorphisms of T helper cell cytokine-associated genes and survival of hemodialysis patients – a prospective study
title Polymorphisms of T helper cell cytokine-associated genes and survival of hemodialysis patients – a prospective study
title_full Polymorphisms of T helper cell cytokine-associated genes and survival of hemodialysis patients – a prospective study
title_fullStr Polymorphisms of T helper cell cytokine-associated genes and survival of hemodialysis patients – a prospective study
title_full_unstemmed Polymorphisms of T helper cell cytokine-associated genes and survival of hemodialysis patients – a prospective study
title_short Polymorphisms of T helper cell cytokine-associated genes and survival of hemodialysis patients – a prospective study
title_sort polymorphisms of t helper cell cytokine-associated genes and survival of hemodialysis patients – a prospective study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5437603/
https://www.ncbi.nlm.nih.gov/pubmed/28525983
http://dx.doi.org/10.1186/s12882-017-0582-x
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