Am. J. Respir. Crit. Care Med., Volume 165, Number 8, April 2002, 1103-1106

Severity of Meningococcal Disease in Children and the Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism

David Harding, Paul B. Baines, David Brull, Vassilis Vassiliou, Ian Ellis, Anthony Hart, Alistair P. J. Thomson, Steve E. Humphries, and Hugh E. Montgomery

Peter Dunn Neonatal Intensive Care Unit and Department of Child Health, University of Bristol, Bristol; Paediatric Intensive Care Unit, Royal Liverpool Children's Hospital, Liverpool; Centre for Cardiovascular Genetics, Department of Medicine, University College London Medical School, London; Institute of Child Health, Royal Liverpool Children's Hospital, Liverpool; and University Department of Medical Microbiology, University of Liverpool, Liverpool, United Kingdom

Critical illness outcome may be causally related to inflammatory response severity. Given that tissue angiotensin-converting-enzyme (ACE) regulates such responses and that the deletion (D) [rather than insertion (I)] variant of the ACE gene is associated with higher tissue ACE levels, DD genotype might be associated with a poorer outcome in a uniform infectious disease state. Illness severity (Pediatric RIsk of Mortality score, the Glasgow Meningococcal Septicaemia Prognostic Score [GMSPS], and clinical course) was recorded for consecutive white patients with meningococcal disease (n = 110, 34 DD genotype, 61 male, aged 49.4 ± 5.4 months) referred to the Royal Liverpool Children's Hospital, UK. Compared with children with  I allele, DD genotype was associated with 14% higher predicted risk of mortality (p = 0.038), higher GMSPS (DD 9.4 ± 0.5, ID/II 7.7± 0.4 [mean ± SEM], p = 0.013), greater prevalence of inotropic support (76% versus 55%, p = 0.03) and ventilation (82% versus 63%, p = 0.04), and longer Pediatric Intensive Care Unit (PICU) stay (5.8 versus 3.9, p = 0.02). DD genotype frequency was 6% (1 case) for the 18 children who did not require PICU care, 33% for the 84 PICU survivors, and 45% for those who died (p = 0.01). ACE DD is associated with increased illness severity in meningococcal disease.

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