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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

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  • Margit Hørup Larsen
  • Anders Albrechtsen
  • Lise Wegner Thørner
  • Thomas Werge
  • Thomas Hansen
  • Ulrik Gether
  • Eva Haastrup
  • Henrik Ullum

Abstract

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

Suggested Citation

  • Margit Hørup Larsen & Anders Albrechtsen & Lise Wegner Thørner & Thomas Werge & Thomas Hansen & Ulrik Gether & Eva Haastrup & Henrik Ullum, 2013. "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," PLOS ONE, Public Library of Science, vol. 8(6), pages 1-6, June.
    • Handle: RePEc:plo:pone00:0066262
    DOI: 10.1371/journal.pone.0066262
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