title: Complement factor H variants I890 and L1007 while commonly associated with atypical hemolytic uremic syndrome are polymorphisms with no functional significance.
abstract: Mutations and polymorphisms in the gene-encoding factor H (CFH) are associated with atypical hemolytic uremic syndrome, dense deposit disease, and age-related macular degeneration. Many of these CFH genetic variations disrupt the regulatory role of factor H, supporting the concept that dysregulation of complement is a unifying pathogenic feature of these disorders. Evidence of a causal relationship with the disease is, however, not available for all CFH genetic variations found in patients, which is a potential cause of misinterpretations with important consequences for the patients and their relatives. CFH I890 and L1007 are two genetic variations repeatedly associated with atypical hemolytic uremic syndrome and also found in patients with dense deposit disease and age-related macular degeneration. Here we report an extensive genetic and functional analysis of these CFH variants. Our results indicate that I890 and L1007 segregate together as part of a distinct and relatively infrequent CFH haplotype in Caucasians. Extensive analysis of the S890/V1007 (control) and I890/L1007 (disease-associated) factor H protein variants failed to provide evidence that these amino acid changes have functional implications. Thus, the presence of the I890 and L1007 variants in healthy individuals and their high frequency in sub-Saharan African and African-American populations strongly suggest that I890 and L1007 are rare factor H polymorphisms unrelated to disease.
authors: Departamento de Medicina Celular y Molecular, Centro de Investigaciones Biológicas (CSIC), Ramiro de Maeztu 9, Madrid, Spain.
authors: Agustín
authors: A
authors: Tortajada
authors: Sheila
authors: S
authors: Pinto
authors: Jorge
authors: J
authors: Martínez-Ara
authors: Margarita
authors: M
authors: López-Trascasa
authors: Pilar
authors: P
authors: Sánchez-Corral
authors: Santiago Rodríguez
authors: SR
authors: de Córdoba
mesh_terms: D000328:Adult; D017954:Africa South of the Sahara; D001741:Black or African American / Q000235:genetics; D019943:Amino Acid Substitution; D065766:Atypical Hemolytic Uremic Syndrome; D044383:Black People / Q000235:genetics; D002675:Child, Preschool; D017242:Complement Factor H / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015432:Glomerulonephritis, Membranoproliferative / Q000235:genetics; D006239:Haplotypes; D006463:Hemolytic-Uremic Syndrome / Q000097:blood / Q000235:genetics*; D006801:Humans; D007223:Infant; D008268:Macular Degeneration / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D013030:Spain
chemical_list: C493495:CFH protein, human; D017242:Complement Factor H