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Open Access 01-10-2011 | Research

IL17A genetic variation is associated with altered susceptibility to Gram-positive infection and mortality of severe sepsis

Authors: Taka-aki Nakada, James A Russell, John H Boyd, Keith R Walley

Published in: Critical Care | Issue 5/2011

Abstract

Introduction

Interleukin 17A (IL17A) plays a key role in host defense against microbial infection including Gram-positive bacteria. Genetic factors contribute to the host defense, but the role of IL17A single nucleotide polymorphisms (SNPs) has not yet been investigated in severe sepsis. Therefore, we hypothesized that SNPs in the IL17A gene alter susceptibility to infection and clinical outcome of severe sepsis.

Methods

We tested for the association of IL17A SNPs with susceptibility to infection and clinical outcome of severe sepsis using two cohorts of European ancestry (derivation cohort, St Paul's Hospital (SPH), n = 679; validation cohort, Vasopressin and Septic Shock Trial (VASST), n = 517). The primary outcome variable was susceptibility to Gram-positive bacterial infection. The secondary outcome variable was 28-day mortality.

Results

Of four tested IL17A tag SNPs (rs4711998, rs8193036, rs2275913, rs1974226), rs1974226 SNP was associated with altered susceptibility to Gram-positive infection in the derivation SPH cohort (corrected P = 0.014). Patients having the rs1974226 GG genotype were more susceptible to Gram-positive infection, compared to AG/AA genotype in the two cohorts of severe sepsis (SPH, P = 0.0036, odds ratio (OR) 2.19, 95% confidence interval (CI) 1.28-3.72; VASST, P = 0.011, OR 1.95, 95%CI 1.16-3.27) and in the subgroup having lung infection (P = 0.017, OR 1.90, 95%CI 1.12-3.21). Furthermore, the IL17A rs1974226 G allele was associated with increased 28-day mortality in two cohorts (SPH, adjusted OR 1.44, 95%CI 1.04-2.02, P = 0.029; VASST, adjusted OR 1.67, 95%CI 1.17-2.40, P = 0.0052).

Conclusions

IL17A genetic variation is associated with altered susceptibility to Gram-positive infection and 28-day mortality of severe sepsis.

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Title: IL17A genetic variation is associated with altered susceptibility to Gram-positive infection and mortality of severe sepsis
Authors: Taka-aki Nakada
James A Russell
John H Boyd
Keith R Walley
Publication date: 01-10-2011
Publisher: BioMed Central
Published in: Critical Care / Issue 5/2011
Electronic ISSN: 1364-8535
DOI: https://doi.org/10.1186/cc10515

Keynote webinar | Spotlight on medication adherence

Springer Medicine

IL17A genetic variation is associated with altered susceptibility to Gram-positive infection and mortality of severe sepsis

Abstract

Introduction

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusions

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