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

• Published in: Respiratory medicine 2010-03, Vol.104 (3), p.440-447
• Main Authors: Solé-Violán, Jordi, Rodríguez de Castro, Felipe, García-Laorden, M. Isabel, Blanquer, José, Aspa, Javier, Borderías, Luis, Briones, M. Luisa, Rajas, Olga, Martín-Loeches Carrondo, Ignacio, Marcos-Ramos, José Alberto, Ferrer Agüero, José María, Garcia-Saavedra, Ayoze, Fiuza, M. Dolores, Caballero-Hidalgo, Araceli, Rodriguez-Gallego, Carlos
• Format: Article
• Language: English
• Subjects: Acquisitions & mergers; Aged; Biological and medical sciences; Community-Acquired Infections - genetics; Community-acquired pneumonia; Confidence intervals; Cytokines; Drug therapy; Genetic polymorphisms; Genetic Predisposition to Disease - genetics; Genotype; Genotype & phenotype; Hospitals; Humans; Intensive care; Interleukin-6 - genetics; Lymphotoxin-alpha - genetics; Male; Medical sciences; Middle Aged; Mortality; Multivariate analysis; Outcome; Pneumology; Pneumonia - genetics; Pneumonia - physiopathology; Polymorphism, Single Nucleotide - genetics; Prognosis; Prospective Studies; Pulmonary/Respiratory; Receptors, Tumor Necrosis Factor - genetics; Respiratory distress syndrome; Respiratory system : syndromes and miscellaneous diseases; Sepsis; Severity of Illness Index; Statistical analysis; Susceptibility; Treatment Outcome; Tumor Necrosis Factor-alpha - genetics
• ISSN: 0954-6111; 1532-3064
• DOI: 10.1016/j.rmed.2009.10.009

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 86 bp 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.