Harding, D and Baines, PB and Brull, D and Vassiliou, V and Ellis, I and Hart, A and Thomson, APJ and Humphries, SE and Montgomery, HE (2002) Severity of meningococcal disease in children and the anglotensin-converting enzyme insertion/deletion polymorphism. AM J RESP CRIT CARE , 165 (8) 1103 - 1106. 10.1164/rccm.2108089.
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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 (1)] 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 greater than or equal to 1 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.
|Title:||Severity of meningococcal disease in children and the anglotensin-converting enzyme insertion/deletion polymorphism|
|Keywords:||ACE, polymorphism, meningococcus, MORTALITY PRISM SCORE, ANGIOTENSIN-II, INTERSTITIAL INFLAMMATION, MONONUCLEAR-CELLS, PEDIATRIC RISK, ACE-INHIBITION, RAT MODEL, GENE, METABOLISM, CAPTOPRIL|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of) > Clinical Physiology|
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
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