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, Hugh E. Montgomery

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Abstract

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.
Original languageEnglish
Pages (from-to)1103-1106
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume165
Issue number8
DOIs
Publication statusPublished - 15 Apr 2002

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