Ninety-day survival rate of patients with sepsis relates to programmed cell death 1 genetic polymorphism rs11568821.
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.
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.
Ashham
A
Mansur
José
J
Hinz
Bronja
B
Hillebrecht
Ingo
I
Bergmann
Aron Frederik
AF
Popov
Michael
M
Ghadimi
Martin
M
Bauer
Tim
T
Beissbarth
Sabine
S
Mihm
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D061026:Programmed Cell Death 1 Receptor; D018805:Sepsis / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D015996:Survival Rate / Q000639:trends; D013997:Time Factors; D055815:Young Adult
C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor