title: Severity of meningococcal disease in children and the angiotensin-converting enzyme insertion/deletion polymorphism.
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 > 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.
authors.affiliation: Peter Dunn Neonatal Intensive Care Unit and Department of Child Health, University of Bristol, Bristol, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Harding
authors.forename: Paul B
authors.initials: PB
authors.lastname: Baines
authors.forename: David
authors.initials: D
authors.lastname: Brull
authors.forename: Vassilis
authors.initials: V
authors.lastname: Vassiliou
authors.forename: Ian
authors.initials: I
authors.lastname: Ellis
authors.forename: Anthony
authors.initials: A
authors.lastname: Hart
authors.forename: Alistair P J
authors.initials: AP
authors.lastname: Thomson
authors.forename: Steve E
authors.initials: SE
authors.lastname: Humphries
authors.forename: Hugh E
authors.initials: HE
authors.lastname: Montgomery
mesh_terms: D001483:Base Sequence; D002675:Child, Preschool; D004251:DNA Transposable Elements; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008589:Meningococcal Infections / Q000235:genetics* / Q000401:mortality; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D011379:Prognosis; D012307:Risk Factors; D017384:Sequence Deletion; D015996:Survival Rate
chemical_list: D004251:DNA Transposable Elements; D007703:Peptidyl-Dipeptidase A