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Genome-Wide Association Study of Genetic Variants in LPS-Stimulated IL-6, IL-8, IL-10, IL-1ra and TNF-α Cytokine Response in a Danish Cohort

BACKGROUND: Cytokine response plays a vital role in various human lipopolysaccharide (LPS) infectious and inflammatory diseases. This study aimed to find genetic variants that might affect the levels of LPS-induced interleukin (IL)-6, IL-8, IL-10, IL-1ra and tumor necrosis factor (TNF)-α cytokine pr...

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Autores principales: Larsen, Margit Hørup, Albrechtsen, Anders, Thørner, Lise Wegner, Werge, Thomas, Hansen, Thomas, Gether, Ulrik, Haastrup, Eva, Ullum, Henrik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3688878/
https://www.ncbi.nlm.nih.gov/pubmed/23823136
http://dx.doi.org/10.1371/journal.pone.0066262
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author Larsen, Margit Hørup
Albrechtsen, Anders
Thørner, Lise Wegner
Werge, Thomas
Hansen, Thomas
Gether, Ulrik
Haastrup, Eva
Ullum, Henrik
author_facet Larsen, Margit Hørup
Albrechtsen, Anders
Thørner, Lise Wegner
Werge, Thomas
Hansen, Thomas
Gether, Ulrik
Haastrup, Eva
Ullum, Henrik
author_sort Larsen, Margit Hørup
collection PubMed
description BACKGROUND: Cytokine response plays a vital role in various human lipopolysaccharide (LPS) infectious and inflammatory diseases. This study aimed to find genetic variants that might affect the levels of LPS-induced interleukin (IL)-6, IL-8, IL-10, IL-1ra and tumor necrosis factor (TNF)-α cytokine production. METHODS: We performed an initial genome-wide association study using Affymetrix Human Mapping 500 K GeneChip® to screen 130 healthy individuals of Danish descent. The levels of IL-6, IL-8, IL-10, IL-1ra and TNF-α in 24-hour LPS-stimulated whole blood samples were compared within different genotypes. The 152 most significant SNPs were replicated using Illumina Golden Gate® GeneChip in an independent cohort of 186 Danish individuals. Next, 9 of the most statistical significant SNPs were replicated using PCR-based genotyping in an independent cohort of 400 Danish individuals. All results were analyzed in a combined study among the 716 Danish individuals. RESULTS: Only one marker of the 500 K Gene Chip in the discovery study showed a significant association with LPS-induced IL-1ra cytokine levels after Bonferroni correction (P<10(−7)). However, this SNP was not associated with the IL-1ra cytokine levels in the replication dataset. No SNPs reached genome-wide significance for the five cytokine levels in the combined analysis of all three stages. CONCLUSIONS: The associations between the genetic variants and the LPS-induced IL-6, IL-8, IL-10, IL-1ra and TNF-α cytokine levels were not significant in the meta-analysis. This present study does not support a strong genetic effect of LPS-stimulated cytokine production; however, the potential for type II errors should be considered.
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spelling pubmed-36888782013-07-02 Genome-Wide Association Study of Genetic Variants in LPS-Stimulated IL-6, IL-8, IL-10, IL-1ra and TNF-α Cytokine Response in a Danish Cohort Larsen, Margit Hørup Albrechtsen, Anders Thørner, Lise Wegner Werge, Thomas Hansen, Thomas Gether, Ulrik Haastrup, Eva Ullum, Henrik PLoS One Research Article BACKGROUND: Cytokine response plays a vital role in various human lipopolysaccharide (LPS) infectious and inflammatory diseases. This study aimed to find genetic variants that might affect the levels of LPS-induced interleukin (IL)-6, IL-8, IL-10, IL-1ra and tumor necrosis factor (TNF)-α cytokine production. METHODS: We performed an initial genome-wide association study using Affymetrix Human Mapping 500 K GeneChip® to screen 130 healthy individuals of Danish descent. The levels of IL-6, IL-8, IL-10, IL-1ra and TNF-α in 24-hour LPS-stimulated whole blood samples were compared within different genotypes. The 152 most significant SNPs were replicated using Illumina Golden Gate® GeneChip in an independent cohort of 186 Danish individuals. Next, 9 of the most statistical significant SNPs were replicated using PCR-based genotyping in an independent cohort of 400 Danish individuals. All results were analyzed in a combined study among the 716 Danish individuals. RESULTS: Only one marker of the 500 K Gene Chip in the discovery study showed a significant association with LPS-induced IL-1ra cytokine levels after Bonferroni correction (P<10(−7)). However, this SNP was not associated with the IL-1ra cytokine levels in the replication dataset. No SNPs reached genome-wide significance for the five cytokine levels in the combined analysis of all three stages. CONCLUSIONS: The associations between the genetic variants and the LPS-induced IL-6, IL-8, IL-10, IL-1ra and TNF-α cytokine levels were not significant in the meta-analysis. This present study does not support a strong genetic effect of LPS-stimulated cytokine production; however, the potential for type II errors should be considered. Public Library of Science 2013-06-18 /pmc/articles/PMC3688878/ /pubmed/23823136 http://dx.doi.org/10.1371/journal.pone.0066262 Text en © 2013 Larsen 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Larsen, Margit Hørup
Albrechtsen, Anders
Thørner, Lise Wegner
Werge, Thomas
Hansen, Thomas
Gether, Ulrik
Haastrup, Eva
Ullum, Henrik
Genome-Wide Association Study of Genetic Variants in LPS-Stimulated IL-6, IL-8, IL-10, IL-1ra and TNF-α Cytokine Response in a Danish Cohort
title Genome-Wide Association Study of Genetic Variants in LPS-Stimulated IL-6, IL-8, IL-10, IL-1ra and TNF-α Cytokine Response in a Danish Cohort
title_full Genome-Wide Association Study of Genetic Variants in LPS-Stimulated IL-6, IL-8, IL-10, IL-1ra and TNF-α Cytokine Response in a Danish Cohort
title_fullStr Genome-Wide Association Study of Genetic Variants in LPS-Stimulated IL-6, IL-8, IL-10, IL-1ra and TNF-α Cytokine Response in a Danish Cohort
title_full_unstemmed Genome-Wide Association Study of Genetic Variants in LPS-Stimulated IL-6, IL-8, IL-10, IL-1ra and TNF-α Cytokine Response in a Danish Cohort
title_short Genome-Wide Association Study of Genetic Variants in LPS-Stimulated IL-6, IL-8, IL-10, IL-1ra and TNF-α Cytokine Response in a Danish Cohort
title_sort genome-wide association study of genetic variants in lps-stimulated il-6, il-8, il-10, il-1ra and tnf-α cytokine response in a danish cohort
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3688878/
https://www.ncbi.nlm.nih.gov/pubmed/23823136
http://dx.doi.org/10.1371/journal.pone.0066262
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