IL17A genetic variation is associated with altered susceptibility to Gram-positive infection and mortality of severe sepsis.
BACKGROUND
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.
University of British Columbia, Critical Care Research Laboratories, Heart + Lung Institute, St. Paul's Hospital, 1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada.
Taka-aki
TA
Nakada
James A
JA
Russell
John H
JH
Boyd
Keith R
KR
Walley
D000368:Aged; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D016908:Gram-Positive Bacterial Infections / Q000235:genetics*; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D018805:Sepsis / Q000235:genetics* / Q000401:mortality
D020381:Interleukin-17