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

Harding, David, Baines, Paul B., Brull, David, Vassiliou, Vassilis, Ellis, Ian, Hart, Anthony, Thomson, Alistair P. J., Humphries, Steve E. and Montgomery, Hugh E. (2002) Severity of Meningococcal Disease in Children and the Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism. American Journal of Respiratory and Critical Care Medicine, 165 (8). pp. 1103-1106. ISSN 1073-449X

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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.

Item Type: Article
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: Pure Connector
Date Deposited: 29 Jun 2017 09:29
Last Modified: 25 Jul 2018 13:46
URI: https://ueaeprints.uea.ac.uk/id/eprint/63965
DOI: 10.1164/ajrccm.165.8.2108089

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