title: Genetic risk factors in typical haemolytic uraemic syndrome.
abstract: BACKGROUND
  Haemolytic uraemic syndrome (HUS) is a disorder characterized by thrombotic microangiopathy, which is caused in 'typical forms' by gastrointestinal infections with Escherichia Coli species that produce verotoxins. Several studies have identified negative prognostic factors of the disease, among which prolonged oliguria, neurological involvement and increased leukocytosis have been more consistently reported. We have hypothesized that the genetic background may also predispose to the development of typical forms of HUS and may influence the clinical course of the disease.
  
  
  METHODS
  Fourteen polymorphisms, known to influence the coagulation pathway or the activity of the renin-angiotensin system, have been selected and studied in 150 Italian children with typical forms of HUS. Two hundred healthy Italian children were used as controls.
  
  
  RESULTS
  The risk of developing HUS was strongly associated with the platelet glycoprotein 1balpha 145M allele (OR 3.08; CI: 1.62-5.85) (P < 0.001). A significant association was also found with polymorphisms located in the adipocyte-derived leucine aminopeptidase and factor V genes. A longer duration of dialysis was moderately associated with increased leukocytosis and with the 807T allele of the platelet glycoprotein 1a gene. High white blood cell count was also strongly associated with the risk of long-term sequelae (OR 2.91, CI: 1.21-6.98) (P < 0.02), whereas the 1166C allele of the angiotensin II type 1 receptor had a significant protective effect (OR 0.28, CI: 0.09-0.83) (P < 0.02).
  
  
  CONCLUSIONS
  These results highlight the role of glycoprotein 1balpha in the physiopathology of typical forms of HUS and show that the genetic background plays a role in the susceptibility and severity of the disease.
authors.affiliation: Division of Nephrology and Dialysis, Bambino Gesù Children's Hospital and Research Institute, Rome.
authors.forename: Anna
authors.initials: A
authors.lastname: Taranta
authors.forename: Alessandra
authors.initials: A
authors.lastname: Gianviti
authors.forename: Alessia
authors.initials: A
authors.lastname: Palma
authors.forename: Veronica
authors.initials: V
authors.lastname: De Luca
authors.forename: Liliana
authors.initials: L
authors.lastname: Mannucci
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Procaccino
authors.forename: Gian Marco
authors.initials: GM
authors.lastname: Ghiggeri
authors.forename: Gianluca
authors.initials: G
authors.lastname: Caridi
authors.forename: Doriana
authors.initials: D
authors.lastname: Fruci
authors.forename: Silvia
authors.initials: S
authors.lastname: Ferracuti
authors.forename: Alfonso
authors.initials: A
authors.lastname: Ferretti
authors.forename: Carmine
authors.initials: C
authors.lastname: Pecoraro
authors.forename: Maurizio
authors.initials: M
authors.lastname: Gaido
authors.forename: Rosa
authors.initials: R
authors.lastname: Penza
authors.forename: Alberto
authors.initials: A
authors.lastname: Edefonti
authors.forename: Luisa
authors.initials: L
authors.lastname: Murer
authors.forename: Alberto E
authors.initials: AE
authors.lastname: Tozzi
authors.forename: Francesco
authors.initials: F
authors.lastname: Emma
mesh_terms: D000293:Adolescent; D000483:Alleles; D000626:Aminopeptidases / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005165:Factor V / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006463:Hemolytic-Uremic Syndrome / Q000097:blood / Q000209:etiology / Q000235:genetics* / Q000628:therapy; D006801:Humans; D007223:Infant; D039421:Integrin alpha2 / Q000235:genetics; D007558:Italy; D008297:Male; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000235:genetics; D015778:Minor Histocompatibility Antigens; D019038:Platelet Glycoprotein GPIb-IX Complex; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D006435:Renal Dialysis; D012307:Risk Factors; D054323:Shiga-Toxigenic Escherichia coli / Q000472:pathogenicity
chemical_list: D039421:Integrin alpha2; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D015778:Minor Histocompatibility Antigens; D019038:Platelet Glycoprotein GPIb-IX Complex; D044140:Receptor, Angiotensin, Type 1; C094990:adhesion receptor; D005165:Factor V; D000626:Aminopeptidases; C464841:ERAP1 protein, human