Genetic variability in the severity and outcome of community-acquired pneumonia.
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.
Solé-Violán
Jordi
J
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
de Castro
Felipe v
Fv
García-Laorden
M Isabel
MI
Blanquer
José
J
Aspa
Javier
J
Borderías
Luis
L
Briones
M Luisa
ML
Rajas
Olga
O
Carrondo
Ignacio Martín-Loeches
IM
Marcos-Ramos
José Alberto
JA
Ferrer Agüero
José María
JM
Garcia-Saavedra
Ayoze
A
Fiuza
M Dolores
MD
Caballero-Hidalgo
Araceli
A
Rodriguez-Gallego
Carlos
C
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*
D015850:Interleukin-6; D008233:Lymphotoxin-alpha; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha