Effects of the 34C>T Variant of the AMPD1 Gene on Immune Function, Multi-Organ Dysfunction, and Mortality in Sepsis Patients.
Shock
; 44(6): 542-7, 2015 Dec.
Article
em En
| MEDLINE
| ID: mdl-26529652
ABSTRACT
INTRODUCTION:
Adenosine exerts anti-inflammatory and tissue-protective effects during systemic inflammation. While the tissue-protective effects might limit organ damage, its anti-inflammatory properties may induce immunoparalysis and impede bacterial clearance. The common 34C>T loss-of-function variant of AMPD1 (rs17602729) is associated with increased adenosine formation, but effects on immune function and outcome in sepsis patients are unknown.METHODS:
The effects of the presence of the 34C>T variant on sepsis susceptibility, immune function, multi-organ dysfunction, and mortality in septic patients were studied. Patients suffering from community acquired pneumonia (CAP, initial cohort nâ=â285; replication cohort nâ=â212) and ventilator-associated pneumonia (VAP, nâ=â117; nâ=â33) and control patients without infection (nâ=â101) were enrolled. Genetic distributions of the AMPD1 SNP were CC 76%, CT 22%, and TT 2% in the initial cohort and CC 80%, CT 18%, and TT 2% in the replication cohort.RESULTS:
The occurrence of septic CAP, but not septic VAP, was increased for the CT versus CC genotype (OR (95% CI) 2.0 (1.1-3.7); Pâ=â0.02) in the initial cohort. The increased risk for the CT versus CC genotype was also observed in the replication cohort but did not reach statistical significance there (Pâ=â0.38), resulting in an OR of the total group of 1.7 (95% CI 1.0-3.1), Pâ=â0.07. In septic patients carrying the CT genotype, the ex vivo production of TNF-α by LPS-stimulated monocytes was attenuated (Pâ=â0.005), indicative of a more pronounced immunoparalytic state in these patients.CONCLUSIONS:
Presence of the AMPD1 34C>T variant is associated with higher infection susceptibility to CAP, but not to VAP. More pronounced immunoparalysis in these patients mediated by the anti-inflammatory effects of adenosine may account for this observation.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
4_TD
/
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Sepse
/
Polimorfismo de Nucleotídeo Único
/
AMP Desaminase
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Insuficiência de Múltiplos Órgãos
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Shock
Ano de publicação:
2015
Tipo de documento:
Article