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

Abstract

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 Grampositive 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.