title: Genetic analysis of the complement factor H related 5 gene in haemolytic uraemic syndrome.
abstract: Several mutations in the CFH gene have been described in non-Shiga-toxin-associated haemolytic uraemic syndrome (non-Stx-HUS), a rare syndrome characterized by haemolytic anaemia, thrombocytopenia and acute renal failure. Mutations in genes encoding other complement regulatory proteins, membrane cofactor protein (CD46) and complement factor I (CFI), were also involved in the pathogenesis of the disease. Anyway, mutations in the three genes account for no more than 50% of cases of non-Stx-HUS. Human complement factor H related 5 (CFHR5) is a recently characterised member of the human complement factor H (CFH) family that has been found as a component of immune deposits in human kidney with sclerotic lesions from different causes. CFHR5 possesses cofactor activity and has been proposed to play a role in complement regulation in the glomerulus. We screened CFHR5 gene for variations potentially involved in the aetiology of HUS. Forty-five patients with HUS and 80 controls were analysed. Altogether, 5 genetic variants in CFHR5 were found in overall 9/45 HUS patients and in 4/80 controls. Statistical analysis showed that allelic variants in CFHR5 were prefentially associated with HUS. Based on these data, we conclude that, though not causative, CFHR5 genetic alterations may play a secondary role in the pathogenesis of HUS.
authors.affiliation: Transplant Research Center Chiara Cucchi de Alessandri e Gilberto Crespi, Mario Negri Institute for Pharmacological Research, Villa Camozzi, Via Privata Camozzi 3, 24020 Ranica, Bergamo, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Monteferrante
authors.forename: S
authors.initials: S
authors.lastname: Brioschi
authors.forename: J
authors.initials: J
authors.lastname: Caprioli
authors.forename: G
authors.initials: G
authors.lastname: Pianetti
authors.forename: P
authors.initials: P
authors.lastname: Bettinaglio
authors.forename: E
authors.initials: E
authors.lastname: Bresin
authors.forename: G
authors.initials: G
authors.lastname: Remuzzi
authors.forename: M
authors.initials: M
authors.lastname: Noris
mesh_terms: D000483:Alleles; D001798:Blood Proteins / Q000235:genetics*; D003172:Complement C1 / Q000235:genetics; D003165:Complement System Proteins; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D006463:Hemolytic-Uremic Syndrome / Q000235:genetics*; D006801:Humans; D009154:Mutation; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D001798:Blood Proteins; C432223:CFHR5 protein, human; D003172:Complement C1; D003165:Complement System Proteins