title: Elevated membrane attack complex in human choroid with high risk complement factor H genotypes.
abstract: Data from human genetics, histopathology, and animal models reveal a major role for the complement system in the development of age-related macular degeneration (AMD). Genetic variations in the complement factor H (CFH) gene are associated with an elevated risk of AMD. In this study we sought to determine whether eyes from donors with a high-risk genotype (homozygosity for the histidine allele at codon 402) exhibit altered levels of membrane attack complex (MAC) in the choroid, compared to eyes with a low risk genotype (homozygosity for tyrosine). Proteins were extracted from the RPE/choroid of 18 donors (10 low risk and 8 high risk) and levels of MAC were assessed using an ELISA assay. Eyes from donors homozygous for the histidine allele showed 69% higher levels of MAC than those homozygous for the tyrosine allele (p < 0.05), independent of whether the eyes showed signs of early AMD. Our results provide evidence that high-risk CFH genotypes may affect AMD risk by increased deposition of MAC around the aging choriocapillaris.
authors: University of Iowa, 4135E MERF, 375 Newton Rd, Iowa City, IA 52242, United States. robert-mullins@uiowa.edu
authors: Robert F
authors: RF
authors: Mullins
authors: Aaron D
authors: AD
authors: Dewald
authors: Luan M
authors: LM
authors: Streb
authors: Kai
authors: K
authors: Wang
authors: Markus H
authors: MH
authors: Kuehn
authors: Edwin M
authors: EM
authors: Stone
mesh_terms: D000368:Aged; D002829:Choroid / Q000378:metabolism*; D017242:Complement Factor H / Q000235:genetics; D015938:Complement Membrane Attack Complex / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics* / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D014019:Tissue Donors
chemical_list: C493495:CFH protein, human; D015938:Complement Membrane Attack Complex; D017242:Complement Factor H