Journal
CRITICAL CARE
Volume 15, Issue 5, Pages -Publisher
BIOMED CENTRAL LTD
DOI: 10.1186/cc10515
Keywords
-
Categories
Funding
- Heart and Stroke Foundation
- Ferring
- Astra Zeneca
- Sirius Genomics Inc
- Sirius Genomics
- Novartis
- Eli Lilly
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available