Figure 1. A single nucleotide polymorphism in TLR4 is associated with S. aureus-induced cytokine release.

A: IL-1ra, IL-1β, IL-6, IL-8, IL-10, TNF-α, G-CSF, and MCP-1 were measured in plasma supernatants by multiplex bead assay after stimulation of fresh whole blood from 300 healthy individuals with heat killed S. aureus 2.5×10⁷ CFU/ml (SA low) or 5 × 10⁷ CFU/ml (SA high) for six hours at 37°C. Data are displayed on a log scale. Boxes show the median and interquartile range; whiskers show upper and lower adjacent values; outside values are not shown for clarity. All mediators induced by S. aureus are significantly greater than in unstimulated blood (P<0.001 for all). B: Cluster dendrogram created from relatedness scores calculated from pairwise comparisons between cytokines induced by stimulation of whole blood with S. aureus 2.5×10⁷ CFU/ml used to derive a composite outcome measure of TNF-α, IL-6, IL-8, G-CSF and IL-1β responses. C: QQ plot (expected versus observed log10 (1/p values)) for the association of 43 single nucleotide polymorphisms with the composite outcome of S. aureus induced cytokine levels demonstrating several lower than expected p values (higher than expected log₁₀ (1/p values)). The lowest p value is rs1927907, an intronic single nucleotide polymorphism in TLR4.