{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T14:30:47Z","timestamp":1773757847424,"version":"3.50.1"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2002,4,1]],"date-time":"2002-04-01T00:00:00Z","timestamp":1017619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2002,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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 \u00b1 5.4 months) referred to the Royal Liverpool Children's Hospital, UK. Compared with children with \u2265 I allele, DD genotype was associated with 14% higher predicted risk of mortality (p = 0.038), higher GMSPS (DD 9.4 \u00b1 0.5, ID\/II 7.7 \u00b1 0.4 [mean \u00b1 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.<\/jats:p>","DOI":"10.1164\/ajrccm.165.8.2108089","type":"journal-article","created":{"date-parts":[[2013,4,4]],"date-time":"2013-04-04T15:04:38Z","timestamp":1365087878000},"page":"1103-1106","source":"Crossref","is-referenced-by-count":71,"title":["Severity of Meningococcal Disease in Children and the Angiotensin-Converting Enzyme Insertion\/Deletion Polymorphism"],"prefix":"10.1093","volume":"165","author":[{"given":"David","family":"Harding","sequence":"first","affiliation":[{"name":"Peter Dunn Neonatal Intensive Care Unit and Department of Child Health, University of Bristol, Bristol; Paediatric Intensive Care Unit, Royal Liverpool Children's Hospital, Liverpool; Centre for Cardiovascular Genetics, Department of Medicine, University College London Medical School, London; Institute of Child Health, Royal Liverpool Children's Hospital, Liverpool; and University Department of Medical Microbiology, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul B.","family":"Baines","sequence":"additional","affiliation":[{"name":"Peter Dunn Neonatal Intensive Care Unit and Department of Child Health, University of Bristol, Bristol; Paediatric Intensive Care Unit, Royal Liverpool Children's Hospital, Liverpool; Centre for Cardiovascular Genetics, Department of Medicine, University College London Medical School, London; Institute of Child Health, Royal Liverpool Children's Hospital, Liverpool; and University Department of Medical Microbiology, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Brull","sequence":"additional","affiliation":[{"name":"Peter Dunn Neonatal Intensive Care Unit and Department of Child Health, University of Bristol, Bristol; Paediatric Intensive Care Unit, Royal Liverpool Children's Hospital, Liverpool; Centre for Cardiovascular Genetics, Department of Medicine, University College London Medical School, London; Institute of Child Health, Royal Liverpool Children's Hospital, Liverpool; and University Department of Medical Microbiology, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vassilis","family":"Vassiliou","sequence":"additional","affiliation":[{"name":"Peter Dunn Neonatal Intensive Care Unit and Department of Child Health, University of Bristol, Bristol; Paediatric Intensive Care Unit, Royal Liverpool Children's Hospital, Liverpool; Centre for Cardiovascular Genetics, Department of Medicine, University College London Medical School, London; Institute of Child Health, Royal Liverpool Children's Hospital, Liverpool; and University Department of Medical Microbiology, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian","family":"Ellis","sequence":"additional","affiliation":[{"name":"Peter Dunn Neonatal Intensive Care Unit and Department of Child Health, University of Bristol, Bristol; Paediatric Intensive Care Unit, Royal Liverpool Children's Hospital, Liverpool; Centre for Cardiovascular Genetics, Department of Medicine, University College London Medical School, London; Institute of Child Health, Royal Liverpool Children's Hospital, Liverpool; and University Department of Medical Microbiology, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony","family":"Hart","sequence":"additional","affiliation":[{"name":"Peter Dunn Neonatal Intensive Care Unit and Department of Child Health, University of Bristol, Bristol; Paediatric Intensive Care Unit, Royal Liverpool Children's Hospital, Liverpool; Centre for Cardiovascular Genetics, Department of Medicine, University College London Medical School, London; Institute of Child Health, Royal Liverpool Children's Hospital, Liverpool; and University Department of Medical Microbiology, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alistair P. J.","family":"Thomson","sequence":"additional","affiliation":[{"name":"Peter Dunn Neonatal Intensive Care Unit and Department of Child Health, University of Bristol, Bristol; Paediatric Intensive Care Unit, Royal Liverpool Children's Hospital, Liverpool; Centre for Cardiovascular Genetics, Department of Medicine, University College London Medical School, London; Institute of Child Health, Royal Liverpool Children's Hospital, Liverpool; and University Department of Medical Microbiology, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steve E.","family":"Humphries","sequence":"additional","affiliation":[{"name":"Peter Dunn Neonatal Intensive Care Unit and Department of Child Health, University of Bristol, Bristol; Paediatric Intensive Care Unit, Royal Liverpool Children's Hospital, Liverpool; Centre for Cardiovascular Genetics, Department of Medicine, University College London Medical School, London; Institute of Child Health, Royal Liverpool Children's Hospital, Liverpool; and University Department of Medical Microbiology, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hugh E.","family":"Montgomery","sequence":"additional","affiliation":[{"name":"Peter Dunn Neonatal Intensive Care Unit and Department of Child Health, University of Bristol, Bristol; Paediatric Intensive Care Unit, Royal Liverpool Children's Hospital, Liverpool; Centre for Cardiovascular Genetics, Department of Medicine, University College London Medical School, London; Institute of Child Health, Royal Liverpool Children's Hospital, Liverpool; and University Department of Medical Microbiology, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2002,4,15]]},"reference":[{"key":"2026031623152684900_B1","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1161\/01.CIR.92.6.1387","article-title":"Angiotensin-converting enzyme in the human heart: effect of the deletion\/insertion polymorphism.","volume":"92","author":"Danser","year":"1995","journal-title":"Circulation"},{"key":"2026031623152684900_B2","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1161\/01.CIR.99.12.1593","article-title":"Pulmonary capillary endothelium-bound angiotensin-converting enzyme activity in humans.","volume":"30","author":"Orfanos","year":"1999","journal-title":"Circulation"},{"key":"2026031623152684900_B3","first-page":"12","article-title":"Angiotensin-converting enzyme (kininase II) mRNA production and enzymatic activity in human peripheral blood monocytes are induced by GM-CSF but not by other cytokines.","volume":"1226","author":"Lazarus","year":"1994","journal-title":"Biochem Biophys Acta"},{"key":"2026031623152684900_B4","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1097\/00024382-200003000-00004","article-title":"Differential effects of short-term ACE- and AT1-receptor inhibition on postischaemic injury and leukocyte adherence in vivo and in vitro.","volume":"13","author":"Guba","year":"2000","journal-title":"Shock"},{"key":"2026031623152684900_B5","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0165-2478(98)00025-X","article-title":"Captopril and lisinopril suppress production of interleukin-12 in human peripheral blood mononuclear cells.","volume":"62","author":"Constantinescu","year":"1998","journal-title":"Immunol Lett"},{"key":"2026031623152684900_B6","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S0304-3940(00)01184-8","article-title":"Goodman DB, Hilliard B, Wysocka M, Cohen JA. 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