title: Genetic variability in the severity and outcome of community-acquired pneumonia.
abstract: BACKGROUND
  Several studies have investigated single nucleotide polymorphisms (SNP) in candidate genes associated with susceptibility, severity or outcome in patients with community-acquired pneumonia (CAP) with conflicting results.
  
  
  METHODS
  Multi-centre, prospective observational study. We studied 1162 white Spanish patients with CAP and 1413 controls. Severe forms of sepsis were recorded in 325 patients. Subjects were genotyped for the following polymorphisms: TNF -238 and -308, LTA +252, IL6 -174, IL1RN 86bp variable number of tandem repeats and TNFRSF1B+676 (TNFR2 M196R).
  
  
  RESULTS
  No significant differences in genotype or allele frequencies were seen among patients and controls. We did not find any association between TNF, LTA, IL6 and IL1RN polymorphisms with disease severity or outcome. Analysis of 28-day mortality showed a significant difference in the distribution of TNFRSF1B+676 G/T genotypes (p=0.0129). Sequential Kaplan-Meier survival analysis of TNFRSF1B+676 G/T polymorphism showed a protective role of the GT genotype. Cox regression analysis adjusted for age, gender, hospital of origin and comorbidities showed that patients with GT genotypes had lower mortality rates compared to patients with GG or TT genotypes (p=0.02; HR 0.53; 95% CI 0.31-0.90 for 90-day survival; p=0.01; HR 0.41; 95% CI 0.21-0.81 for 28-day survival and p=0.049; HR 0.48; 95% CI 0.23-0.997 for 15-day survival).
  
  
  CONCLUSIONS
  Our study does not support a role for the controversial studied polymorphisms of the TNF, LTA, IL6 and IL1RN genes in the susceptibility or outcome of CAP. A protective role of heterozygosity for the functionally relevant TNFRSF1B+676 polymorphism in the outcome of CAP was observed.
authors.affiliation: Intensive Care Unit, Hospital Universitario de Gran Canaria Dr Negrín, Barranco de la Ballena S/N, 35020 Las Palmas de Gran Canaria, Spain. jrodgal@gobiernodecanarias.org
authors.forename: Jordi
authors.initials: J
authors.lastname: Solé-Violán
authors.forename: Felipe v
authors.initials: Fv
authors.lastname: de Castro
authors.forename: M Isabel
authors.initials: MI
authors.lastname: García-Laorden
authors.forename: José
authors.initials: J
authors.lastname: Blanquer
authors.forename: Javier
authors.initials: J
authors.lastname: Aspa
authors.forename: Luis
authors.initials: L
authors.lastname: Borderías
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Briones
authors.forename: Olga
authors.initials: O
authors.lastname: Rajas
authors.forename: Ignacio Martín-Loeches
authors.initials: IM
authors.lastname: Carrondo
authors.forename: José Alberto
authors.initials: JA
authors.lastname: Marcos-Ramos
authors.forename: José María
authors.initials: JM
authors.lastname: Ferrer Agüero
authors.forename: Ayoze
authors.initials: A
authors.lastname: Garcia-Saavedra
authors.forename: M Dolores
authors.initials: MD
authors.lastname: Fiuza
authors.forename: Araceli
authors.initials: A
authors.lastname: Caballero-Hidalgo
authors.forename: Carlos
authors.initials: C
authors.lastname: Rodriguez-Gallego
mesh_terms: D000368:Aged; D017714:Community-Acquired Infections / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D008233:Lymphotoxin-alpha / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000235:genetics* / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D015850:Interleukin-6; D008233:Lymphotoxin-alpha; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha