Donor genetic variants in interleukin-6 and interleukin-6 receptor associate with biopsy-proven rejection following kidney transplantation

Abstract Rejection after kidney transplantation remains an important cause of allograft failure that markedly impacts morbidity. Cytokines are a major player in rejection, and we, therefore, explored the impact of interleukin-6 (IL6) and IL-6 receptor (IL6R) gene polymorphisms on the occurrence of r...

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Autores principales:	Felix Poppelaars, Mariana Gaya da Costa, Siawosh K. Eskandari, Jeffrey Damman, Marc A. Seelen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/93961bfdfaa14ed48733f6d83499c6ae
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spelling	oai:doaj.org-article:93961bfdfaa14ed48733f6d83499c6ae2021-12-02T19:06:38ZDonor genetic variants in interleukin-6 and interleukin-6 receptor associate with biopsy-proven rejection following kidney transplantation10.1038/s41598-021-95714-z2045-2322https://doaj.org/article/93961bfdfaa14ed48733f6d83499c6ae2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95714-zhttps://doaj.org/toc/2045-2322Abstract Rejection after kidney transplantation remains an important cause of allograft failure that markedly impacts morbidity. Cytokines are a major player in rejection, and we, therefore, explored the impact of interleukin-6 (IL6) and IL-6 receptor (IL6R) gene polymorphisms on the occurrence of rejection after renal transplantation. We performed an observational cohort study analyzing both donor and recipient DNA in 1271 renal transplant‐pairs from the University Medical Center Groningen in The Netherlands and associated single nucleotide polymorphisms (SNPs) with biopsy-proven rejection after kidney transplantation. The C-allele of the IL6R SNP (Asp358Ala; rs2228145 A > C, formerly rs8192284) in donor kidneys conferred a reduced risk of rejection following renal transplantation (HR 0.78 per C-allele; 95%-CI 0.67–0.90; P = 0.001). On the other hand, the C-allele of the IL6 SNP (at position-174 in the promoter; rs1800795 G > C) in donor kidneys was associated with an increased risk of rejection for male organ donors (HR per C-allele 1.31; 95%-CI 1.08–1.58; P = 0.0006), but not female organ donors (P = 0.33). In contrast, neither the IL6 nor IL6R SNP in the recipient showed an association with renal transplant rejection. In conclusion, donor IL6 and IL6R genotypes but not recipient genotypes represent an independent prognostic marker for biopsy-proven renal allograft rejection.Felix PoppelaarsMariana Gaya da CostaSiawosh K. EskandariJeffrey DammanMarc A. SeelenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Felix Poppelaars Mariana Gaya da Costa Siawosh K. Eskandari Jeffrey Damman Marc A. Seelen Donor genetic variants in interleukin-6 and interleukin-6 receptor associate with biopsy-proven rejection following kidney transplantation
description	Abstract Rejection after kidney transplantation remains an important cause of allograft failure that markedly impacts morbidity. Cytokines are a major player in rejection, and we, therefore, explored the impact of interleukin-6 (IL6) and IL-6 receptor (IL6R) gene polymorphisms on the occurrence of rejection after renal transplantation. We performed an observational cohort study analyzing both donor and recipient DNA in 1271 renal transplant‐pairs from the University Medical Center Groningen in The Netherlands and associated single nucleotide polymorphisms (SNPs) with biopsy-proven rejection after kidney transplantation. The C-allele of the IL6R SNP (Asp358Ala; rs2228145 A > C, formerly rs8192284) in donor kidneys conferred a reduced risk of rejection following renal transplantation (HR 0.78 per C-allele; 95%-CI 0.67–0.90; P = 0.001). On the other hand, the C-allele of the IL6 SNP (at position-174 in the promoter; rs1800795 G > C) in donor kidneys was associated with an increased risk of rejection for male organ donors (HR per C-allele 1.31; 95%-CI 1.08–1.58; P = 0.0006), but not female organ donors (P = 0.33). In contrast, neither the IL6 nor IL6R SNP in the recipient showed an association with renal transplant rejection. In conclusion, donor IL6 and IL6R genotypes but not recipient genotypes represent an independent prognostic marker for biopsy-proven renal allograft rejection.
format	article
author	Felix Poppelaars Mariana Gaya da Costa Siawosh K. Eskandari Jeffrey Damman Marc A. Seelen
author_facet	Felix Poppelaars Mariana Gaya da Costa Siawosh K. Eskandari Jeffrey Damman Marc A. Seelen
author_sort	Felix Poppelaars
title	Donor genetic variants in interleukin-6 and interleukin-6 receptor associate with biopsy-proven rejection following kidney transplantation
title_short	Donor genetic variants in interleukin-6 and interleukin-6 receptor associate with biopsy-proven rejection following kidney transplantation
title_full	Donor genetic variants in interleukin-6 and interleukin-6 receptor associate with biopsy-proven rejection following kidney transplantation
title_fullStr	Donor genetic variants in interleukin-6 and interleukin-6 receptor associate with biopsy-proven rejection following kidney transplantation
title_full_unstemmed	Donor genetic variants in interleukin-6 and interleukin-6 receptor associate with biopsy-proven rejection following kidney transplantation
title_sort	donor genetic variants in interleukin-6 and interleukin-6 receptor associate with biopsy-proven rejection following kidney transplantation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/93961bfdfaa14ed48733f6d83499c6ae
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Donor genetic variants in interleukin-6 and interleukin-6 receptor associate with biopsy-proven rejection following kidney transplantation

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