@article{3127123,
    title = "Association of autophagy-related 16-like 1 (ATG16L1) gene polymorphism with sepsis severity in patients with sepsis and ventilator-associated pneumonia",
    author = "Savva, A. and Plantinga, T.S. and Kotanidou, A. and Farcas, M. and Baziaka, F. and Raftogiannis, M. and Orfanos, S.E. and Dimopoulos, G. and Netea, M.G. and Giamarellos-Bourboulis, E.J.",
    journal = "European Journal of Clinical Microbiology and Infectious Diseases",
    year = "2014",
    volume = "33",
    number = "9",
    pages = "1609-1614",
    publisher = "Springer-Verlag",
    doi = "10.1007/s10096-014-2118-7",
    keywords = "lipopolysaccharide;  procalcitonin;  tumor necrosis factor alpha;  ATG16L1 protein, human;  calcitonin;  carrier protein;  procalcitonin;  protein precursor;  tumor necrosis factor alpha, Acinetobacter baumannii;  APACHE;  article;  ATG16L1 gene;  autophagy;  bacterium isolate;  blood oxygen tension;  disease course;  disease severity;  Enterobacter aerogenes;  Enterobacter cloacae;  enzyme linked immunosorbent assay;  gene;  gene frequency;  genetic association;  genotype;  heterozygote;  human;  human tissue;  Klebsiella pneumoniae;  monocyte;  multicenter study (topic);  priority journal;  Proteus mirabilis;  Providencia stuartii;  Pseudomonas aeruginosa;  septic shock;  Sequential Organ Failure Assessment Score;  single nucleotide polymorphism;  Staphylococcus aureus;  Stenotrophomonas maltophilia;  ventilated patient;  ventilator associated pneumonia;  adolescent;  adult;  aged;  blood;  clinical trial;  female;  genetic polymorphism;  genetic predisposition;  genetics;  genotyping technique;  male;  middle aged;  multicenter study;  pathology;  secretion (process);  sepsis;  ventilator associated pneumonia;  very elderly;  young adult, Adolescent;  Adult;  Aged;  Aged, 80 and over;  Calcitonin;  Carrier Proteins;  Female;  Genetic Predisposition to Disease;  Genotype;  Genotyping Techniques;  Humans;  Male;  Middle Aged;  Pneumonia, Ventilator-Associated;  Polymorphism, Genetic;  Protein Precursors;  Sepsis;  Tumor Necrosis Factor-alpha;  Young Adult",
    abstract = "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-α (TNF-α) 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-α 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. © 2014 Springer-Verlag."
}