title: Allelic variants of complement genes associated with dense deposit disease.
abstract: The alternative pathway of the complement cascade plays a role in the pathogenesis of dense deposit disease (DDD). Deficiency of complement factor H and mutations in CFH associate with the development of DDD, but it is unknown whether allelic variants in other complement genes also associate with this disease. We studied patients with DDD and identified previously unreported sequence alterations in several genes in addition to allelic variants and haplotypes common to patients with DDD. We found that the likelihood of developing DDD increases with the presence of two or more risk alleles in CFH and C3. To determine the functional consequence of this finding, we measured the activity of the alternative pathway in serum samples from phenotypically normal controls genotyped for variants in CFH and C3. Alternative pathway activity was higher in the presence of variants associated with DDD. Taken together, these data confirm that DDD is a complex genetic disease and may provide targets for the development of disease-specific therapies.
authors.affiliation: Interdisciplinary PhD Program in Genetics, University of Iowa, Iowa City, Iowa, USA.
authors.forename: Maria Asuncion
authors.initials: MA
authors.lastname: Abrera-Abeleda
authors.forename: Carla
authors.initials: C
authors.lastname: Nishimura
authors.forename: Kathy
authors.initials: K
authors.lastname: Frees
authors.forename: Michael
authors.initials: M
authors.lastname: Jones
authors.forename: Tara
authors.initials: T
authors.lastname: Maga
authors.forename: Louis M
authors.initials: LM
authors.lastname: Katz
authors.forename: Yuzhou
authors.initials: Y
authors.lastname: Zhang
authors.forename: Richard J H
authors.initials: RJ
authors.lastname: Smith
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001706:Biopsy; D003167:Complement Activation / Q000235:genetics; D003176:Complement C3 / Q000235:genetics; D003165:Complement System Proteins / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D015432:Glomerulonephritis, Membranoproliferative / Q000209:etiology / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D011110:Polymorphism, Genetic; D012306:Risk
chemical_list: D003176:Complement C3; D003165:Complement System Proteins