Genetic risk factors in typical haemolytic uraemic syndrome.
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.
Taranta
Anna
A
Division of Nephrology and Dialysis, Bambino Gesù Children's Hospital and Research Institute, Rome.
Gianviti
Alessandra
A
Palma
Alessia
A
De Luca
Veronica
V
Mannucci
Liliana
L
Procaccino
Maria Antonietta
MA
Ghiggeri
Gian Marco
GM
Caridi
Gianluca
G
Fruci
Doriana
D
Ferracuti
Silvia
S
Ferretti
Alfonso
A
Pecoraro
Carmine
C
Gaido
Maurizio
M
Penza
Rosa
R
Edefonti
Alberto
A
Murer
Luisa
L
Tozzi
Alberto E
AE
Emma
Francesco
F
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
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