PT - JOURNAL ARTICLE AU - M A Abrera-Abeleda AU - C Nishimura AU - J L H Smith AU - S Sethi AU - J L McRae AU - B F Murphy AU - G Silvestri AU - C Skerka AU - M Józsi AU - P F Zipfel AU - G S Hageman AU - R J H Smith TI - Variations in the complement regulatory genes factor H (CFH) and factor H related 5 (<em>CFHR5</em>) are associated with membranoproliferative glomerulonephritis type II (dense deposit disease) AID - 10.1136/jmg.2005.038315 DP - 2006 Jul 01 TA - Journal of Medical Genetics PG - 582--589 VI - 43 IP - 7 4099 - http://jmg.bmj.com/content/43/7/582.short 4100 - http://jmg.bmj.com/content/43/7/582.full SO - J Med Genet2006 Jul 01; 43 AB - 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.