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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.

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