title: Variations in the complement regulatory genes factor H (CFH) and factor H related 5 (CFHR5) are associated with membranoproliferative glomerulonephritis type II (dense deposit disease).
abstract: BACKGROUND
  Membranoproliferative glomerulonephritis type II or dense deposit disease (MPGN II/DDD) causes chronic renal dysfunction that progresses to end stage renal disease in about half of patients within 10 years of diagnosis. Deficiency of and mutations in the complement factor H (CFH) gene are associated with the development of MPGN II/DDD, suggesting that dysregulation of the alternative pathway of the complement cascade is important in disease pathophysiology.
  
  
  METHODS
  Patients with MPGN II/DDD were studied to determine whether specific allele variants of CFH and CFHR5 segregate preferentially with the MPGN II/DDD disease phenotype. The control group was compromised of 131 people in whom age related macular degeneration had been excluded.
  
  
  RESULTS
  Allele frequencies of four single nucleotide polymorphisms in CFH and three in CFHR5 were significantly different between MPGN II/DDD patients and controls.
  
  
  CONCLUSIONS
  We have identified specific allele variants of CFH and CFHR5 associated with the MPGN II/DDD disease phenotype. While our data can be interpreted to further implicate complement in the pathogenesis of MPGN II/DDD, these associations could also be unrelated to disease pathophysiology. Functional studies are required to resolve this question.
authors.affiliation: Department of Otolaryngology, Division of Nephrology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Abrera-Abeleda
authors.forename: C
authors.initials: C
authors.lastname: Nishimura
authors.forename: J L H
authors.initials: JL
authors.lastname: Smith
authors.forename: S
authors.initials: S
authors.lastname: Sethi
authors.forename: J L
authors.initials: JL
authors.lastname: McRae
authors.forename: B F
authors.initials: BF
authors.lastname: Murphy
authors.forename: G
authors.initials: G
authors.lastname: Silvestri
authors.forename: C
authors.initials: C
authors.lastname: Skerka
authors.forename: M
authors.initials: M
authors.lastname: Józsi
authors.forename: P F
authors.initials: PF
authors.lastname: Zipfel
authors.forename: G S
authors.initials: GS
authors.lastname: Hageman
authors.forename: R J H
authors.initials: RJ
authors.lastname: Smith
mesh_terms: D001706:Biopsy; D001798:Blood Proteins / Q000235:genetics*; D017242:Complement Factor H / Q000235:genetics*; D003165:Complement System Proteins; D017931:DNA Primers; D017353:Gene Deletion; D005787:Gene Frequency; D014644:Genetic Variation; D015432:Glomerulonephritis, Membranoproliferative / Q000145:classification / Q000235:genetics* / Q000473:pathology; D006801:Humans; D009154:Mutation; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values
chemical_list: D001798:Blood Proteins; C432223:CFHR5 protein, human; D017931:DNA Primers; D017242:Complement Factor H; D003165:Complement System Proteins