Journal Article

Variants at the promoter of the interleukin-6 gene are associated with severity and outcome of pneumococcal community-acquired pneumonia

Rodríguez-Gallego, Carlos, Ferrer-Agüero, José María, González-Quevedo, Nereida, Solé-Violán, Jordi, Borderías, Luis, Blanquer, José, Briones, M. Luisa, García-Laorden, M. Isabel, Rodríguez de Castro, Felipe, Herrera-Ramos, Estefanía, Aspa, Javier, Martín-Loeches, Ignacio, Marcos-Ramos, José Alberto, Sologuren, Ithaisa, Rajas, Olga, Noda, Judith

2012

Overview

Purpose Conflicting results about the role of genetic variability at IL6 , particularly the -174 G/C single nucleotide polymorphism (SNP), in sepsis have been reported. We studied the genetic variability at IL6 in patients with community-acquired pneumonia (CAP) and pneumococcal CAP (P-CAP). Methods This was a multicenter, prospective observational study. IL6 -174 was analyzed in 1,227 white Spanish patients with CAP (306 with P-CAP). IL6 1753 C/G ( N  = 750), 2954 G/C ( N  = 845), and haplotypes defined by these SNPs were also studied. Results In CAP patients the genotype -174 GG were associated with protection against acute respiratory distress syndrome (ARDS) ( p  = 0.008, OR = 0.4, 95% CI 0.2–0.8). No other significant associations were observed. However, in patients with P-CAP multivariate analysis adjusted for age, gender, co-morbidity, hospital of origin, and severity (pneumonia severity index, PSI) showed that the IL6 -174 GG genotype was protective against the development of ARDS ( p  = 0.002, OR = 0.25, 95% CI 0.07–0.79), septic shock ( p  = 0.006, OR = 0.46, 95% CI 0.18–0.79), and multiple organ dysfunction syndrome ( p  = 0.02, OR = 0.53, 95% CI 0.27–0.89). P-CAP patients homozygous for IL6 -174 G also showed a higher survival in a logistic regression analysis adjusted for age, gender, co-morbidity, hospital of origin, and PSI ( p  = 0.048, OR = 0.27, 95% CI 0.07–0.98). Conclusions Our results indicate that the IL-6 -174 GG genotype is associated with lower severity and mortality in patients with P-CAP. This effect was higher than that observed in patients with CAP irrespective of the causal pathogen involved. Our results highlight the importance of the causal pathogen in genetic epidemiological studies in sepsis.

• Publisher: Springer-Verlag,Springer,Springer Nature B.V
• Subject: Analysis / Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy / Anesthesiology / Antigens / Biological and medical sciences / Community-Acquired Infections - genetics / Community-Acquired Infections - mortality / Comorbidity / Critical Care Medicine / Cytokines / Disease / Emergency and intensive cardiocirculatory care. Cardiogenic shock. Coronary intensive care / Emergency Medicine / Female / Genetic aspects / Genotype & phenotype / Haplotypes / Hospital Mortality / Hospitals / Humans / Intensive / Intensive care / Intensive care medicine / Interleukin 6 / Interleukin-6 - genetics / Male / Medical colleges / Medical sciences / Medicine / Medicine & Public Health / Middle Aged / Mortality / Multiple organ dysfunction syndrome / Multivariate analysis / Original / Pain Medicine / Pathogens / Pediatrics / Pneumology/Respiratory System / Pneumonia / Pneumonia, Pneumococcal - genetics / Pneumonia, Pneumococcal - mortality / Polymorphism / Polymorphism, Genetic / Promoter Regions, Genetic / Promoters / Prospective Studies / Regression analysis / Respiratory distress syndrome / Sepsis / Septic shock / Severity of Illness Index / Single nucleotide polymorphisms / Single-nucleotide polymorphism / Streptococcus infections / Streptococcus pneumoniae / Survival