2011
DOI: 10.1159/000323880
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A Nonsynonymous Polymorphism of IRAK4 Associated with Increased Prevalence of Gram-Positive Infection and Decreased Response to Toll-Like Receptor Ligands

Abstract: Mutations in IRAK4 have been associated with recurrent Gram-positive infections in children. Given the central role of IRAK4 in innate immunity signaling, we hypothesized that common genetic variants of IRAK4 may be associated with prevalence of Gram-positive infection in critically ill adults. Haplotype clade tag single nucleotide polymorphisms (SNPs) of the IRAK4 gene were selected and genotyped in a cohort of 1,029 critically ill patients with systemic inflammatory response syndrome (SIRS). We found that a … Show more

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Cited by 19 publications
(21 citation statements)
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References 94 publications
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“…Hyporesponsiveness in this system, as recently demonstrated for an association between IRAK4 polymorphisms and susceptibility to Gram-positive infections in patients with critical illness, limit the effectiveness of the innate immune responses (56). We show that direct exposure of A549 cells to pneumococci induces only low-level CXCL8 secretion.…”
Section: Discussionsupporting
confidence: 62%
“…Hyporesponsiveness in this system, as recently demonstrated for an association between IRAK4 polymorphisms and susceptibility to Gram-positive infections in patients with critical illness, limit the effectiveness of the innate immune responses (56). We show that direct exposure of A549 cells to pneumococci induces only low-level CXCL8 secretion.…”
Section: Discussionsupporting
confidence: 62%
“…A polymorphism in CD14, a key molecule in the innate immune response to Gram-negative endotoxin has been found to increase the risk of serious Gram-negative infections [34], while polymorphisms in the complement-activating mannose-binding lectin results in increased serious infections [34]. A functional polymorphism of IRAK4 increases the risk of Gram-positive infections in childhood and in adult septic shock [36]. …”
Section: Sepsis In the Era Of The Meta-genomementioning
confidence: 99%
“…ly ill patients with systemic inflammatory response syndrome, a haplotype clade tagged by the A allele of the htSNP G29429A (Ala428Thr) was associated with an increased relative risk of Gram-positive infection at admission to the ICU [4] . One effect of this genotype was a decreased IL-6 production in response to PAMPs.…”
Section: Editorialmentioning
confidence: 99%