Genetic risk factors in typical haemolytic uraemic syndrome

Anna Taranta, Alessandra Gianviti, Alessia Palma, Veronica De Luca, Liliana Mannucci, Maria Antonietta Procaccino, Gian Marco Ghiggeri, Gianluca Caridi, Doriana Fruci, Silvia Ferracuti, Alfonso Ferretti, Carmine Pecoraro, Maurizio Gaido, Rosa Penza, Alberto Edefonti, Luisa Murer, Alberto E. Tozzi, Francesco Emma

Research output: Contribution to journalArticle

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 1bα 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 1bα 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.

Original languageEnglish
Pages (from-to)1851-1857
Number of pages7
JournalNephrology Dialysis Transplantation
Volume24
Issue number6
DOIs
Publication statusPublished - Jun 2009

Keywords

  • Coagulation
  • Haemolytic uraemic syndrome
  • Polymorphisms
  • Renin-angiotensin system

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

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    Taranta, A., Gianviti, A., Palma, A., De Luca, V., Mannucci, L., Procaccino, M. A., Ghiggeri, G. M., Caridi, G., Fruci, D., Ferracuti, S., Ferretti, A., Pecoraro, C., Gaido, M., Penza, R., Edefonti, A., Murer, L., Tozzi, A. E., & Emma, F. (2009). Genetic risk factors in typical haemolytic uraemic syndrome. Nephrology Dialysis Transplantation, 24(6), 1851-1857. https://doi.org/10.1093/ndt/gfn720