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

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 mi...

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Published in:American journal of respiratory and critical care medicine 2002-04, Vol.165 (8), p.1103-1106
Main Authors: Harding, David, Baines, Paul B, Brull, David, Vassiliou, Vassilis, Ellis, Ian, Hart, Anthony, Thomson, Alistair P. J, Humphries, Steve E, Montgomery, Hugh E
Format: Article
Language:English
Subjects:
Bacterial diseases
Bacterial diseases of the respiratory system
Base Sequence
Biological and medical sciences
Child, Preschool
DNA Transposable Elements
Female
Genotype
Human bacterial diseases
Humans
Infectious diseases
Male
Medical sciences
Meningococcal Infections - genetics
Meningococcal Infections - mortality
Peptidyl-Dipeptidase A - genetics
Polymorphism, Genetic
Prognosis
Risk Factors
Sequence Deletion
Survival Rate
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Summary: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 > or = 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.
ISSN:1073-449X
1535-4970
DOI:10.1164/ajrccm.165.8.2108089