PMID- 24791954
OWN - NLM
STAT- MEDLINE
DCOM- 20150401
LR  - 20211021
IS  - 1435-4373 (Electronic)
IS  - 0934-9723 (Linking)
VI  - 33
IP  - 9
DP  - 2014 Sep
TI  - Association of autophagy-related 16-like 1 (ATG16L1) gene polymorphism with 
      sepsis severity in patients with sepsis and ventilator-associated pneumonia.
PG  - 1609-14
LID - 10.1007/s10096-014-2118-7 [doi]
AB  - Autophagy is a highly conserved mechanism of eukaryotic cells implicated in cell 
      homeostasis and elimination of intracellular pathogens. Functional polymorphisms 
      in genes encoding for autophagy have been associated with susceptibility to 
      inflammatory and infectious diseases, but data on severe infections are missing. 
      The aim of the present study was to assess whether polymorphisms in genes 
      encoding proteins involved in autophagy influence susceptibility to 
      ventilator-associated pneumonia (VAP). Mechanically ventilated patients with VAP 
      were studied. Genotyping for autophagy-related 16-like 1 (ATG16L1, rs2241880) 
      functional polymorphism was performed using the TaqMan single-nucleotide assay. 
      Monocytes were isolated from patients and stimulated with lipopolysaccharide 
      (LPS). Tumor necrosis factor-alpha (TNF-alpha) was measured in the supernatants of 
      monocytes using an enzyme-linked immunosorbent assay. Procalcitonin (PCT) was 
      also measured in the serum of patients by an immuno-time-resolved amplified 
      cryptate technology assay. A total of 155 patients with VAP were enrolled in the 
      study. Carriage of the minor A allele of ATG16L1 was associated with septic shock 
      with at least one organ failure (odds ratio (OR): 2.40, p: 0.036). TNF-alpha 
      production was significantly greater among the carriers of the polymorphism 
      presenting with at least one organ failure (p: 0.040). PCT was increased upon 
      worsening to septic shock and organ failure only among carriers of the minor 
      frequency A alleles. In a homogeneous cohort of septic patients with VAP, the 
      carriage of autophagy polymorphisms predisposes to VAP severity and septic shock 
      development. This may be related with predisposition to immunoparalysis.
FAU - Savva, A
AU  - Savva A
AD  - 4th Department of Internal Medicine, Attikon University Hospital, University of 
      Athens, Medical School, 1 Rimini Str., 12462, Athens, Greece, 
      savva.athina@gmail.com.
FAU - Plantinga, T S
AU  - Plantinga TS
FAU - Kotanidou, A
AU  - Kotanidou A
FAU - Farcas, M
AU  - Farcas M
FAU - Baziaka, F
AU  - Baziaka F
FAU - Raftogiannis, M
AU  - Raftogiannis M
FAU - Orfanos, S E
AU  - Orfanos SE
FAU - Dimopoulos, G
AU  - Dimopoulos G
FAU - Netea, M G
AU  - Netea MG
FAU - Giamarellos-Bourboulis, E J
AU  - Giamarellos-Bourboulis EJ
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20140503
PL  - Germany
TA  - Eur J Clin Microbiol Infect Dis
JT  - European journal of clinical microbiology & infectious diseases : official 
      publication of the European Society of Clinical Microbiology
JID - 8804297
RN  - 0 (ATG16L1 protein, human)
RN  - 0 (Autophagy-Related Proteins)
RN  - 0 (CALCA protein, human)
RN  - 0 (Carrier Proteins)
RN  - 0 (Protein Precursors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9007-12-9 (Calcitonin)
RN  - JHB2QIZ69Z (Calcitonin Gene-Related Peptide)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Autophagy-Related Proteins
MH  - Calcitonin/blood
MH  - Calcitonin Gene-Related Peptide
MH  - Carrier Proteins/*genetics
MH  - Female
MH  - *Genetic Predisposition to Disease
MH  - Genotype
MH  - Genotyping Techniques
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Pneumonia, Ventilator-Associated/*pathology
MH  - *Polymorphism, Genetic
MH  - Protein Precursors/blood
MH  - Sepsis/*pathology
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Young Adult
EDAT- 2014/05/06 06:00
MHDA- 2015/04/02 06:00
CRDT- 2014/05/06 06:00
PHST- 2014/02/12 00:00 [received]
PHST- 2014/04/08 00:00 [accepted]
PHST- 2014/05/06 06:00 [entrez]
PHST- 2014/05/06 06:00 [pubmed]
PHST- 2015/04/02 06:00 [medline]
AID - 10.1007/s10096-014-2118-7 [doi]
PST - ppublish
SO  - Eur J Clin Microbiol Infect Dis. 2014 Sep;33(9):1609-14. doi: 
      10.1007/s10096-014-2118-7. Epub 2014 May 3.