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)

M. A. Abrera-Abeleda, C. Nishimura, J. L.H. Smith, S. Sethi, J. L. McRae, B. F. Murphy, G. Silvestri, C. Skerka, M. Józsi, P. F. Zipfel, G. S. Hageman, R. J.H. Smith

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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.

Original languageEnglish (US)
Pages (from-to)582-589
Number of pages8
JournalJournal of medical genetics
Volume43
Issue number7
DOIs
StatePublished - Jul 1 2006

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ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Abrera-Abeleda, M. A., Nishimura, C., Smith, J. L. H., Sethi, S., McRae, J. L., Murphy, B. F., Silvestri, G., Skerka, C., Józsi, M., Zipfel, P. F., Hageman, G. S., & Smith, R. J. H. (2006). 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). Journal of medical genetics, 43(7), 582-589. https://doi.org/10.1136/jmg.2005.038315