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)

• Published in: Journal of medical genetics Vol. 43; no. 7; pp. 582 - 589
• Main 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
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 01.07.2006; BMJ; BMJ Publishing Group LTD; BMJ Group
• Subjects: age related macular degeneration; AMD; Biological and medical sciences; Biopsy; Blood Proteins - genetics; C3 nephritic factor; C3NeF; C4 binding protein; C4BP; Cardiology. Vascular system; CFH; CFHL1; CFI; complement factor H; Complement Factor H - genetics; complement factor H-like protein 1; complement factor H-related 5; complement factor I; complement receptor 1; Complement System Proteins; CR1; DAF; DDD; decay accelerating factor; denaturing high performance liquid chromatography; dense deposit disease; DHPLC; DNA Primers; end stage renal disease; end-stage renal failure; ESRD; GBM; Gene Deletion; Gene Frequency; General aspects. Genetic counseling; Genes; Genetic Variation; Genotype & phenotype; glomerular basement membrane; Glomerulonephritis; Glomerulonephritis, Membranoproliferative - classification; Glomerulonephritis, Membranoproliferative - genetics; Glomerulonephritis, Membranoproliferative - pathology; Humans; Kidney diseases; linkage disequilibrium; Macular degeneration; MCP; Medical genetics; Medical sciences; membrane co-factor protein; membranoproliferative glomerulonephritis type II; membranoproliferative glomerulonephritis types I/II/III; Microscopy; MPGN I/II/III; Mutation; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Original; Pathogenesis; Patients; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Proteins; Reference Values; Rodents; single nucleotide polymorphism; SNP; Studies; Kidney disease; Human; Urinary system disease; Association; Gene; Disease; Variations; Genetics; Complement; Mesangial proliferative glomerulonephritis
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.2005.038315

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.