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Angiotensin-converting enzyme insertion/deletion polymorphism is not associated with susceptibility and outcome in sepsis and acute respiratory distress syndrome

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Abstract

Objective

The insertion/deletion (I/D) of a 289 base pair Alu repeat sequence polymorphism in the angiotensin-converting enzyme gene (ACE) has been shown to predict susceptibility and outcome in the acute respiratory distress syndrome (ARDS). We hypothesized that the I/D polymorphism also confers susceptibility to sepsis and is a predisposing factor for morbidity and mortality of patients with severe sepsis.

Design and setting

Case-control study including 212 consecutive patients fulfilling criteria for severe sepsis admitted to a Spanish network of postsurgical and critical care units, and 364 population-based controls. Susceptibility to severe sepsis was evaluated as primary outcome; mortality in severe sepsis, susceptibility to sepsis-induced ARDS, and mortality in sepsis-induced ARDS were examined as secondary outcomes. An additive model of inheritance in which patients were classified into three genotype groups (II, ID, and DD) was used for association testing.

Measurements and results

Genotype and allele frequencies of I/D were distributed similarly in all septic, ARDS, and non-ARDS patients and in population-based controls. ACE I/D polymorphism was not associated with severe sepsis susceptibility or mortality. The ACE I/D polymorphism was associated neither with sepsis-induced ARDS susceptibility (p = 0.895) or mortality (p = 0.950). These results remained nonsignificant when adjusted for other covariates using multiple logistic regression analysis or Kaplan–Meier estimates of 28-day survival.

Conclusions

Our data do not support an association of the ACE gene I/D polymorphism with susceptibility or mortality in severe sepsis or with sepsis-induced ARDS in Spanish patients.

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Acknowledgements

Members of GEN-SEP are: J. Villar, E. Espinosa, R. Sangüesa, M. Muros, L. Pérez-Méndez, S. Lubillo, N. Maca-Meyer, C. Flores, and P. Tejera. Members of GRECIA are: J. Blanco; A. Muriel; V. Sagrado and J. C. Ballesteros, Medicina Intensiva Hospital Clínico Universitario, Salamanca; F. Taboada and G. Muñiz, Medicina Intensiva, Hospital Central de Asturias, Oviedo; F. Gandía and F. Bobillo, Medicina Intensiva, Hospital Clinico Universitario, Valladolid; L. Tamayo and A. G. Labattut, Medicina Intensiva, Hospital General de Soria, Soria; J. Collado, Medicina Intensiva, Complejo Hospitalario de León, León; M. Valledor and M. T. Antuña, Medicina Intensiva, Hospital San Agustín, Aviles; M. J. López and J. J. Cortina, Medicina Intensiva, Hospital General de Segovia, Segovia; T. Saldaña, A. Caballero, and T. Álvarez, Medicina Intensiva, Hospital Virgen de la Concha, Zamora; M. De Frutos, Medicina Intensiva, Hospital General Yagüe, Burgos; J. Guerra, Medicina Intensiva, Hospital de Cabueñes, Gijón; B. Álvarez and J. Sandoval, Medicina Intensiva, Hospital del Bierzo, Ponferrada.

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Authors and Affiliations

  1. Multidisciplinary Organ Dysfunction Evaluation Research Network (MODERN), Research Unit, Hospital Universitario Dr. Negrin, Barranco de la Ballena, s/n - 4th floor, south wing, 35010, Las Palmas de Gran Canaria, Canary Islands, Spain

    Jesús Villar

  2. Instituto de Salud Carlos III, CIBER de Enfermedades Respiratorias, Madrid, Spain

    Jesús Villar, Carlos Flores, Lina Pérez-Méndez, Jesús Blanco & Mercedes Muros

  3. Keenan Research Center, St. Michael’s Hospital, Toronto, Ontario, Canada

    Jesús Villar & Arthur S. Slutsky

  4. Division of Human Genetics, Research Unit, Hospital Universitario NS de Candelaria, Tenerife, Spain

    Carlos Flores, Nicole Maca-Meyer & Paula Tejera

  5. Department of Medicine, Division of Pulmonary and Critical Care, University of Chicago, Chicago, Ill, USA

    Carlos Flores

  6. Division of Clinical and Genetic Epidemiology, Research Unit, Hospital Universitario NS de Candelaria, Tenerife, Spain

    Lina Pérez-Méndez

  7. Department of Anesthesia, Hospital Universitario NS de Candelaria, Tenerife, Spain

    Elena Espinosa & Ruben Sangüesa

  8. Intensive Care Unit, Hospital Universitario Río Hortega, Valladolid, Spain

    Jesús Blanco & Arturo Muriel

  9. Department of Clinical Biochemistry, Hospital Universitario NS de Candelaria, Tenerife, Spain

    Mercedes Muros

  10. Department of Medicine, Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada

    Arthur S. Slutsky

Authors
  1. Jesús Villar
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  2. Carlos Flores
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  3. Lina Pérez-Méndez
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  4. Nicole Maca-Meyer
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  5. Elena Espinosa
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  6. Jesús Blanco
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  7. Ruben Sangüesa
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  8. Arturo Muriel
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  9. Paula Tejera
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  10. Mercedes Muros
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  11. Arthur S. Slutsky
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Corresponding author

Correspondence to Jesús Villar.

Additional information

This research was supported by grants from FUNCIS (53/04) and the Ministerio de Educación y Ciencia, Spain (SAF2004-06833). J.V. is the principal investigator in both grants.

The authors named above wrote this article on behalf of the GRECIA and GEN-SEP groups. The members of the GRECIA and GEN-SEP groups are listed under Acknowledgements at the end of the article.

J. Villar, C. Flores, and L. Pérez-Méndez contributed equally to this work.

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Villar, J., Flores, C., Pérez-Méndez, L. et al. Angiotensin-converting enzyme insertion/deletion polymorphism is not associated with susceptibility and outcome in sepsis and acute respiratory distress syndrome. Intensive Care Med 34, 488–495 (2008). https://doi.org/10.1007/s00134-007-0937-z

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  • DOI: https://doi.org/10.1007/s00134-007-0937-z

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