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Title: Genetic variability in the severity and outcome of community-acquired pneumonia
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 
UNESCO Clasification: 32 Ciencias médicas
320508 Enfermedades pulmonares
320102 Genética clínica
Keywords: Community-acquired pneumonia
Genetic polymorphisms
Issue Date: 2010
Journal: Respiratory Medicine 
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.
ISSN: 0954-6111
DOI: 10.1016/j.rmed.2009.10.009
Source: Respiratory Medicine [ISSN 0954-6111],v. 104, p. 440-447
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