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IL-17A rs1974226 GG genotype is associated with increased susceptibility to Gram-positive infection and mortality of severe sepsis

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Introduction

IL-17A plays a key role in host defense against microbial infection including Gram-positive bacteria. Genetic factors contribute to the host defense. Whether genetic variation of IL-17A is associated with altered clinical outcome of severe sepsis is unknown.

Methods

We tested for genetic association of IL-17A SNPs with susceptibility to infection and clinical outcome of severe sepsis using two cohorts of European ancestry (St Paul's Hospital (SPH) derivation cohort, n = 679; Vasopressin and Septic Shock Trial (VASST) validation cohort 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 tag SNPs (rs4711998, rs8193036, rs2275913, rs1974226) in the IL-17A gene, rs1974226 SNP was associated with altered susceptibility to Gram-positive bacterial infection in the derivation cohort (corrected P = 0.014). Patients who have the GG genotype of the rs1974226 SNP were more susceptible to Gram-positive bacterial infection, compared to the AG/AA genotype in the two cohorts of severe sepsis (SPH, P = 0.0036; VASST, P = 0.011) and in the subgroup having lung infection (P = 0.017). Furthermore, the G allele of the IL-17A rs1974226 SNP was associated with increased 28-day mortality in two cohorts (SPH, adjusted OR 1.44, 95% CI 1.04 to 2.02, P = 0.029; VASST, adjusted OR 1.67, 95% CI 1.17 to 2.40, P = 0.0052).

Conclusion

IL-17A genetic variation is associated with altered susceptibility to Gram-positive infection and 28-day mortality of severe sepsis.

References

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    Puel A, et al.: Chronic mucocutaneous candidiasis in humans with inborn errors of interleukin-17 immunity. Science 2011, 332: 65-68. 10.1126/science.1200439

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    Cho JS, et al.: IL-17 is essential for host defense against cutaneous Staphylococcus aureus infection in mice. J Clin Invest 2010, 120: 1762-1773. 10.1172/JCI40891

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Author information

Correspondence to T Nakada.

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Nakada, T., Russell, J., Boyd, J. et al. IL-17A rs1974226 GG genotype is associated with increased susceptibility to Gram-positive infection and mortality of severe sepsis. Crit Care 16, P2 (2012). https://doi.org/10.1186/cc10609

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Keywords

  • Severe Sepsis
  • Secondary Outcome Variable
  • Derivation Cohort
  • Shock Trial
  • Altered Susceptibility