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Ninety-Day Survival Rate of Patients With Sepsis Relates to Programmed Cell Death 1 Genetic Polymorphism rs11568821
  1. Ashham Mansur, MD*,
  2. José Hinz, MD*,
  3. Bronja Hillebrecht, MD*,
  4. Ingo Bergmann, MD*,
  5. Aron Frederik Popov, MD,
  6. Michael Ghadimi, MD,
  7. Martin Bauer, MD*,
  8. Tim Beissbarth, PhD§,
  9. Sabine Mihm, PhD
  1. From the Departments of *Anesthesiology, Emergency and Intensive Care Medicine, †Thoracic and Cardiovascular Surgery, ‡General and Visceral Surgery, §Medical Statistics, and ∥Gastroenterology and Endocrinology, University Medical Center Goettingen, Goettingen, Germany.
  1. Received August 1, 2013, and in revised form December 11, 2013.
  2. Accepted for publication December 12, 2013.
  3. Reprints: Sabine Mihm, PhD, University Medical Center Goettingen, Department of Gastroenterology and Endocrinology, Robert-Koch-Straße 40, 37075 Goettingen, Germany. E-mail: smihm{at}med.uni-goettingen.de.
  4. The authors declare no conflicts of interest.

Abstract

Background Sepsis is a life-threatening condition. Programmed cell death 1 protein (PD-1), a negative costimulatory molecule, is suggested to be involved in pathogenesis as mortality is associated with high expression and as neutralizing antibodies improve survival in a mouse model. The PD-1 gene harbors an intronic single-nucleotide polymorphism, rs11568821, which is located in a transcription factor–binding site and supposed to affect PD-1 transcription.

Objective This study aimed at investigating whether mortality (90-day) among patients with sepsis associates with PD-1 rs11568821 genotypes.

Methods Adult white patients with sepsis from the surgical intensive care units of a university medical center were followed up for 90 days, and mortality was recorded as primary outcome variable. Blood samples were taken for PD-1 rs11568821 genotyping. Sequential Organ Failure Assessment scores increased at enrollment and during the observation period to monitor morbidity.

Results Two hundred nineteen critically ill patients with sepsis were enrolled in this investigation. Ninety-day mortality was significantly higher among G homozygotes than among A allele carriers (P = 0.0032). During intensive care unit stay, G homozygotes experienced higher Sequential Organ Failure Assessment scores (P < 0.001) and a higher demand of vasopressor therapy (P = 0.0107).

Conclusions Data provide first associative evidence for PD-1 rs11568821 as a prognostic indicator in patients with sepsis.

Key Words
  • programmed cell death 1 protein
  • single-nucleotide polymorphism (SNP)
  • intensive care
  • anti–PD-1 antibody
  • negative costimulatory molecule
  • 90-day mortality

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