title: Variants at the promoter of the interleukin-6 gene are associated with severity and outcome of pneumococcal community-acquired pneumonia.
abstract: OBJECTIVE
  Conflicting results about the role of genetic variability at IL6, particularly the -174 G/C single nucleotide polymorphism (SNP), in sepsis have been reported. We studied the genetic variability at IL6 in patients with community-acquired pneumonia (CAP) and pneumococcal CAP (P-CAP).
  
  
  METHODS
  This was a multicenter, prospective observational study. IL6 -174 was analyzed in 1,227 white Spanish patients with CAP (306 with P-CAP). IL6 1753 C/G (N = 750), 2954 G/C (N = 845), and haplotypes defined by these SNPs were also studied.
  
  
  RESULTS
  In CAP patients the genotype -174 GG were associated with protection against acute respiratory distress syndrome (ARDS) (p = 0.008, OR = 0.4, 95% CI 0.2-0.8). No other significant associations were observed. However, in patients with P-CAP multivariate analysis adjusted for age, gender, co-morbidity, hospital of origin, and severity (pneumonia severity index, PSI) showed that the  IL6 -174 GG genotype was protective against the development of ARDS (p = 0.002, OR = 0.25, 95% CI 0.07-0.79), septic shock (p = 0.006, OR = 0.46, 95% CI 0.18-0.79), and multiple organ dysfunction syndrome (p = 0.02, OR = 0.53, 95% CI 0.27-0.89). P-CAP patients homozygous for IL6 -174 G also showed a higher survival in a logistic regression analysis adjusted for age, gender, co-morbidity, hospital of origin, and PSI (p = 0.048, OR = 0.27, 95% CI 0.07-0.98).
  
  
  CONCLUSIONS
  Our results indicate that the IL-6 -174 GG genotype is associated with lower severity and mortality in patients with P-CAP. This effect was higher than that observed in patients with CAP irrespective of the causal pathogen involved. Our results highlight the importance of the causal pathogen in genetic epidemiological studies in sepsis.
authors: Critical Care Centre, Corporació Sanitaria Parc Tauli-University Hospital Sabadell, Sabadell, Spain.
authors: Ignacio
authors: I
authors: Martín-Loeches
authors: Jordi
authors: J
authors: Solé-Violán
authors: Felipe
authors: F
authors: Rodríguez de Castro
authors: M Isabel
authors: MI
authors: García-Laorden
authors: Luis
authors: L
authors: Borderías
authors: José
authors: J
authors: Blanquer
authors: Olga
authors: O
authors: Rajas
authors: M Luisa
authors: ML
authors: Briones
authors: Javier
authors: J
authors: Aspa
authors: Estefanía
authors: E
authors: Herrera-Ramos
authors: José Alberto
authors: JA
authors: Marcos-Ramos
authors: Ithaisa
authors: I
authors: Sologuren
authors: Nereida
authors: N
authors: González-Quevedo
authors: José María
authors: JM
authors: Ferrer-Agüero
authors: Judith
authors: J
authors: Noda
authors: Carlos
authors: C
authors: Rodríguez-Gallego
mesh_terms: D017714:Community-Acquired Infections / Q000235:genetics / Q000401:mortality; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011018:Pneumonia, Pneumococcal / Q000235:genetics* / Q000401:mortality; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011446:Prospective Studies; D012720:Severity of Illness Index
chemical_list: D015850:Interleukin-6