title: The development of atypical haemolytic-uraemic syndrome is influenced by susceptibility factors in factor H and membrane cofactor protein: evidence from two independent cohorts.
abstract: BACKGROUND
  In both familial and sporadic atypical haemolytic-uraemic syndrome (aHUS), mutations have been reported in regulators of the alternative complement pathway including factor H (CFH), membrane cofactor protein (MCP), and the serine protease factor I (IF). A characteristic feature of both MCP and CFH associated HUS is reduced penetrance and variable inheritance; one possible explanation for this is that functional changes in complement proteins act as modifiers.
  
  
  OBJECTIVE
  To examine single nucleotide polymorphisms in both CFH and MCP genes in two large cohorts of HUS patients (Newcastle and Paris).
  
  
  RESULTS
  In both cohorts there was an association with HUS for both CFH and MCP alleles. CFH and MCP haplotypes were also significantly different in HUS patients compared with controls.
  
  
  CONCLUSIONS
  This study suggests that there are naturally occurring susceptibility factors in CFH and MCP for the development of atypical HUS.
authors.affiliation: Service d'Immunologie Biologique, Hôpital Européen Georges Pompidou, Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Fremeaux-Bacchi
authors.forename: E J
authors.initials: EJ
authors.lastname: Kemp
authors.forename: J A
authors.initials: JA
authors.lastname: Goodship
authors.forename: M-A
authors.initials: MA
authors.lastname: Dragon-Durey
authors.forename: L
authors.initials: L
authors.lastname: Strain
authors.forename: C
authors.initials: C
authors.lastname: Loirat
authors.forename: H-W
authors.initials: HW
authors.lastname: Deng
authors.forename: T H J
authors.initials: TH
authors.lastname: Goodship
mesh_terms: D000483:Alleles; D015331:Cohort Studies; D017242:Complement Factor H / Q000235:genetics* / Q000378:metabolism; D003165:Complement System Proteins; D017931:DNA Primers / Q000737:chemistry; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006463:Hemolytic-Uremic Syndrome / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D051916:Membrane Cofactor Protein / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011951:Receptors, Complement
chemical_list: D017931:DNA Primers; D051916:Membrane Cofactor Protein; D011951:Receptors, Complement; D017242:Complement Factor H; D003165:Complement System Proteins