Respiratory Medicine
Volume 104, Issue 3 , Pages 440-447, March 2010

Genetic variability in the severity and outcome of community-acquired pneumonia

  • Jordi Solé-Violán

      Affiliations

    • Intensive Care Unit, Hospital Universitario de Gran Canaria Dr Negrín, Barranco de la Ballena S/N, 35020 Las Palmas de Gran Canaria, Spain
    • Corresponding Author InformationCorresponding author. Tel.: +34 928 449 511; fax: +34 928 449293.
    • ,
  • Felipe Rodríguez de Castro

      Affiliations

    • Respiratory Disease Service, Hospital Universitario de Gran Canaria Dr Negrín, Barranco de la Ballena S/N, 35020 Las Palmas de Gran Canaria, Spain
    • ,
  • M. Isabel García-Laorden

      Affiliations

    • Department of Immunology, Hospital Universitario de Gran Canaria Dr Negrín, Barranco de la Ballena S/N, 35020 Las Palmas de Gran Canaria, Spain
    • ,
  • José Blanquer

      Affiliations

    • Intensive Care Unit, Hospital Clínico y Universitario de Valencia, Av. Blasco Ibáñez 17, 46010 Valencia, Spain
    • ,
  • Javier Aspa

      Affiliations

    • Respiratory Disease Service, Hospital Universitario de la Princesa, Diego de León 62, 28006 Madrid, Spain
    • ,
  • Luis Borderías

      Affiliations

    • Respiratory Disease Service, Hospital San Jorge, Av. Martínez Velasco 36, 22071 Huesca, Spain
    • ,
  • M. Luisa Briones

      Affiliations

    • Respiratory Disease Service, Hospital Clínico y Universitario de Valencia, Blasco Ibáñez 17, 46010 Valencia, Spain
    • ,
  • Olga Rajas

      Affiliations

    • Respiratory Disease Service, Hospital Universitario de la Princesa, Diego de León 62, 28006 Madrid, Spain
    • ,
  • Ignacio Martín-Loeches Carrondo

      Affiliations

    • Intensive Care Unit, Hospital Universitario de Gran Canaria Dr Negrín, Barranco de la Ballena S/N, 35020 Las Palmas de Gran Canaria, Spain
    • Critical Care Department, Joan XXIII University Hospital, CIBER Enfermedades Respiratorias (CIBERES), 43007 Tarragona, Spain
    • ,
  • José Alberto Marcos-Ramos

      Affiliations

    • Intensive Care Unit, Hospital Universitario de Gran Canaria Dr Negrín, Barranco de la Ballena S/N, 35020 Las Palmas de Gran Canaria, Spain
    • ,
  • José María Ferrer Agüero

      Affiliations

    • Intensive Care Unit, Hospital Universitario de Gran Canaria Dr Negrín, Barranco de la Ballena S/N, 35020 Las Palmas de Gran Canaria, Spain
    • ,
  • Ayoze Garcia-Saavedra

      Affiliations

    • Department of Immunology, Hospital Universitario de Gran Canaria Dr Negrín, Barranco de la Ballena S/N, 35020 Las Palmas de Gran Canaria, Spain
    • ,
  • M. Dolores Fiuza

      Affiliations

    • Research Unit Hospital, Universitario de Gran Canaria Dr Negrín, Barranco de la Ballena S/N, 35020 Las Palmas de Gran Canaria, Spain
    • ,
  • Araceli Caballero-Hidalgo

      Affiliations

    • Research Unit Hospital, Universitario de Gran Canaria Dr Negrín, Barranco de la Ballena S/N, 35020 Las Palmas de Gran Canaria, Spain
    • ,
  • Carlos Rodriguez-Gallego

      Affiliations

    • Department of Immunology, Hospital Universitario de Gran Canaria Dr Negrín, Barranco de la Ballena S/N, 35020 Las Palmas de Gran Canaria, Spain

Received 29 July 2009; accepted 13 October 2009. published online 09 November 2009.

Summary 

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.

Keywords: Community-acquired pneumonia, Genetic polymorphisms, Susceptibility, Outcome

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PII: S0954-6111(09)00330-8

doi:10.1016/j.rmed.2009.10.009

Respiratory Medicine
Volume 104, Issue 3 , Pages 440-447, March 2010

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