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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

Introduction: 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.

Subjects: 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.

Conclusion: 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.

  • AMD, age related macular degeneration
  • C3NeF, C3 nephritic factor
  • C4BP, C4 binding protein
  • CFH, complement factor H
  • CFHL1, complement factor H-like protein 1
  • CFI, complement factor I
  • CR1, complement receptor 1
  • DAF, decay accelerating factor
  • DDD, dense deposit disease
  • DHPLC, denaturing high performance liquid chromatography
  • ESRD, end stage renal disease
  • GBM, glomerular basement membrane
  • LD, linkage disequilibrium
  • MCP, membrane co-factor protein
  • MPGN I/II/III, membranoproliferative glomerulonephritis types I/II/III
  • SNP, single nucleotide polymorphism
  • membranoproliferative glomerulonephritis type II
  • dense deposit disease
  • complement factor H
  • complement factor H-related 5
  • end-stage renal failure
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