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Cytokine gene polymorphisms and the outcome of invasive candidiasis: a prospective cohort study.

Publication ,  Journal Article
Johnson, MD; Plantinga, TS; van de Vosse, E; Velez Edwards, DR; Smith, PB; Alexander, BD; Yang, JC; Kremer, D; Laird, GM; Oosting, M; Walsh, TJ ...
Published in: Clin Infect Dis
February 15, 2012

BACKGROUND:  Candida bloodstream infections cause significant morbidity and mortality among hospitalized patients. Although clinical and microbiological factors affecting prognosis have been identified, the impact of genetic variation in the innate immune responses mediated by cytokines on outcomes of infection remains to be studied. METHODS:  A cohort of 338 candidemia patients and 351 noninfected controls were genotyped for single-nucleotide polymorphisms (SNPs) in 6 cytokine genes (IFNG, IL10, IL12B, IL18, IL1β, IL8) and 1 cytokine receptor gene (IL12RB1). The association of SNPs with both candidemia susceptibility and outcome were assessed. Concentrations of pro- and antiinflammatory cytokines were measured in in vitro peripheral blood mononuclear cell stimulation assays and in serum from infected patients. RESULTS:  None of the cytokine SNPs studied were associated with susceptibility to candidemia. Persistent fungemia occurred in 13% of cases. In the multivariable model, persistent candidemia was significantly associated with (odds ratio [95% confidence interval]): total parenteral nutrition (2.79 [1.26-6.17]), dialysis dependence (3.76 [1.46-8.64]), and the SNPs IL10 rs1800896 (3.45 [1.33-8.93]) and IL12B rs41292470 (5.36 [1.51-19.0]). In vitro production capacity of interleukin-10 and interferon-γ was influenced by these polymorphisms, and significantly lower proinflammatory cytokine concentrations were measured in serum from patients with persistent fungemia. CONCLUSIONS:  Polymorphisms in IL10 and IL12B that result in low production of proinflammatory cytokines are associated with persistent fungemia in candidemia patients. This provides insights for future targeted management strategies for patients with Candida bloodstream infections.

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Published In

Clin Infect Dis

DOI

EISSN

1537-6591

Publication Date

February 15, 2012

Volume

54

Issue

4

Start / End Page

502 / 510

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Prospective Studies
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Microbiology
  • Male
  • Leukocytes, Mononuclear
  • Humans
  • Genetic Predisposition to Disease
  • Genetic Association Studies
 

Citation

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Chicago
ICMJE
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Johnson, M. D., Plantinga, T. S., van de Vosse, E., Velez Edwards, D. R., Smith, P. B., Alexander, B. D., … Netea, M. G. (2012). Cytokine gene polymorphisms and the outcome of invasive candidiasis: a prospective cohort study. Clin Infect Dis, 54(4), 502–510. https://doi.org/10.1093/cid/cir827
Johnson, Melissa D., Theo S. Plantinga, Esther van de Vosse, Digna R. Velez Edwards, P Brian Smith, Barbara D. Alexander, John C. Yang, et al. “Cytokine gene polymorphisms and the outcome of invasive candidiasis: a prospective cohort study.Clin Infect Dis 54, no. 4 (February 15, 2012): 502–10. https://doi.org/10.1093/cid/cir827.
Johnson MD, Plantinga TS, van de Vosse E, Velez Edwards DR, Smith PB, Alexander BD, et al. Cytokine gene polymorphisms and the outcome of invasive candidiasis: a prospective cohort study. Clin Infect Dis. 2012 Feb 15;54(4):502–10.
Johnson, Melissa D., et al. “Cytokine gene polymorphisms and the outcome of invasive candidiasis: a prospective cohort study.Clin Infect Dis, vol. 54, no. 4, Feb. 2012, pp. 502–10. Pubmed, doi:10.1093/cid/cir827.
Johnson MD, Plantinga TS, van de Vosse E, Velez Edwards DR, Smith PB, Alexander BD, Yang JC, Kremer D, Laird GM, Oosting M, Joosten LAB, van der Meer JWM, van Dissel JT, Walsh TJ, Perfect JR, Kullberg B-J, Scott WK, Netea MG. Cytokine gene polymorphisms and the outcome of invasive candidiasis: a prospective cohort study. Clin Infect Dis. 2012 Feb 15;54(4):502–510.
Journal cover image

Published In

Clin Infect Dis

DOI

EISSN

1537-6591

Publication Date

February 15, 2012

Volume

54

Issue

4

Start / End Page

502 / 510

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Prospective Studies
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Microbiology
  • Male
  • Leukocytes, Mononuclear
  • Humans
  • Genetic Predisposition to Disease
  • Genetic Association Studies