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). Issue 7 (18th November 2005)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Journal of medical genetics. Volume 43:Issue 7(2006)
• Page Start: 582
• Page End: 589
• Publication Date: 2005-11-18
• Subjects: 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; Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmg.2005.038315
• Languages: English
• ISSNs: 1468-6244

Abstract

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.