NDT Advance Access first published online on December 25, 2008
This version published online on January 15, 2009
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfn720
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Genetic risk factors in typical haemolytic uraemic syndrome
1 Division of Nephrology and Dialysis, Bambino Gesù Children's Hospital and Research Institute, Rome 2 Laboratory on Pathophysiology of Uremia, Giannina Gaslini Children's Hospital, Genoa 3 Research Center, Bambino Gesù Children's Hospital, Rome 4 Department of Nephrology and Urology, Santobono Hospital, Naples 5 Division of Pediatric Nephrology, Regina Margherita Children's Hospital, Turin 6 Department of Biomedicine of Developing Age, Pediatric Clinic, University of Bari, Bari 7 Division of Pediatric Nephrology, De Marchi Pediatric Clinic, Maggiore Hospital, Mangiagalli and Regina Elena Foundation, IRCCS, Milan 8 Division of Pediatric Nephrology, Dialysis and Transplantation, Department of Pediatrics, University of Padua, Padua 9 Division of Epidemiology, Bambino Gesù Children's Hospital and Research Institute, Rome, Italy
Correspondence and offprint requests to: Francesco Emma, Department of Nephrology and Urology, Division of Nephrology and Dialysis, Ospedale Bambino Gesù—IRCCS, Piazza S. Onofrio, 4 00165 Rome, Italy. Tel: +39-0668592126; Fax: +39-0668592602; E-mail: emma{at}opbg.net
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Abstract |
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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 1b
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 1b 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.
Keywords: coagulation; haemolytic uraemic syndrome; polymorphisms; renin–angiotensin system
Received for publication: 5. 6.08
Accepted in revised form: 1.12.08