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

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Abstract

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.

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Acknowledgments

The present study was supported by grants from “Fondo de Investigaciones Sanitarias”, Ministerio de Sanidad (FIS 02/1620, 04/1190 and 06/1031) with the funding of European Regional Development Fund-European Social Fund (FEDER-FSE); “Sociedad Española de Neumología y Cirugía Torácica” (SEPAR); RedRespira-ISCIII-RTIC-03/11; FUNCIS, Gobierno de Canarias (04/09); NGQ was supported by FUNCIS (INREDCAN 5/06), MIGL by FUNCIS (Proyecto Biorregion 2006) and EHR by a grant from Universidad de Las Palmas de Gran Canaria.

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Authors and Affiliations

  1. Critical Care Centre, Corporació Sanitaria Parc Tauli-University Hospital Sabadell, Sabadell, Spain

    Ignacio Martín-Loeches

  2. Intensive Care Unit, Hospital Universitario de Gran Canaria Dr Negrín, Las Palmas de Gran Canaria, Spain

    Ignacio Martín-Loeches, Jordi Solé-Violán & José María Ferrer-Agüero

  3. Respiratory Disease Service, Hospital Universitario de Gran Canaria Dr Negrín, Las Palmas de Gran Canaria, Spain

    Felipe Rodríguez de Castro

  4. Department of Medical and Surgical Sciences, School of Medicine, University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain

    Felipe Rodríguez de Castro & Carlos Rodríguez-Gallego

  5. Department of Immunology, Hospital Universitario de Gran Canaria Dr Negrín, Barranco de la Ballena s/n, 35010, Las Palmas de Gran Canaria, Spain

    M. Isabel García-Laorden, Estefanía Herrera-Ramos, Ithaisa Sologuren, Nereida González-Quevedo, Judith Noda & Carlos Rodríguez-Gallego

  6. Respiratory Disease Service, Hospital San Jorge, Huesca, Spain

    Luis Borderías

  7. Intensive Care Unit, Hospital Clínico y Universitario de Valencia, Valencia, Spain

    José Blanquer

  8. Respiratory Disease Service, Hospital Universitario de la Princesa, Madrid, Spain

    Olga Rajas & Javier Aspa

  9. Respiratory Disease Service, Hospital Clínico y Universitario de Valencia, Valencia, Spain

    M. Luisa Briones

  10. Intensive Care Unit, Hospital General José Molina Orosa, Lanzarote, Spain

    José Alberto Marcos-Ramos

  11. Research Unit, Hospital Universitario de Gran Canaria Dr Negrín, Las Palmas de Gran Canaria, Spain

    Judith Noda

Authors
  1. Ignacio Martín-Loeches
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  2. Jordi Solé-Violán
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  3. Felipe Rodríguez de Castro
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  4. M. Isabel García-Laorden
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  5. Luis Borderías
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  6. José Blanquer
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  9. Javier Aspa
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  10. Estefanía Herrera-Ramos
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  11. José Alberto Marcos-Ramos
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  12. Ithaisa Sologuren
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  13. Nereida González-Quevedo
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  14. José María Ferrer-Agüero
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  15. Judith Noda
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  16. Carlos Rodríguez-Gallego
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Corresponding author

Correspondence to Carlos Rodríguez-Gallego.

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Martín-Loeches, I., Solé-Violán, J., Rodríguez de Castro, F. et al. Variants at the promoter of the interleukin-6 gene are associated with severity and outcome of pneumococcal community-acquired pneumonia. Intensive Care Med 38, 256–262 (2012). https://doi.org/10.1007/s00134-011-2406-y

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  • DOI: https://doi.org/10.1007/s00134-011-2406-y

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