title: A Novel Complotype Combination Associates with Age-Related Macular Degeneration and High Complement Activation Levels in vivo.
abstract: The complement system is the first line of defense against foreign intruders, and deregulation of this system has been described in multiple diseases. In age-related macular degeneration (AMD), patients have higher complement activation levels compared to controls. Recently, a combination of three single nucleotide polymorphisms (SNPs) in genes of the complement system, referred to as a complotype, has been described to increase complement activation in vitro. Here we describe a novel complotype composed of CFB (rs4151667)-CFB (rs641153)-CFH (rs800292), which is strongly associated with both AMD disease status (p = 5.84*10(-13)) and complement activation levels in vivo (p = 8.31*10(-9)). The most frequent genotype combination of this complotype was associated with the highest complement activation levels in both patients and controls. These findings are relevant in the context of complement-lowering treatments for AMD that are currently under development. Patients with a genetic predisposition to higher complement activation levels will potentially benefit the most of such treatments.
authors.affiliation: Radboud university medical center, Department of Ophthalmology, Nijmegen, The Netherlands.|Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
authors.forename: Constantin C
authors.initials: CC
authors.lastname: Paun
authors.affiliation: Radboud university medical center, Department of Ophthalmology, Nijmegen, The Netherlands.
authors.forename: Yara T E
authors.initials: YTE
authors.lastname: Lechanteur
authors.affiliation: Radboud university medical center, Department for Health Evidence, Nijmegen, The Netherlands.
authors.forename: Joannes M M
authors.initials: JMM
authors.lastname: Groenewoud
authors.affiliation: University Hospital of Cologne, Department of Ophthalmology, Cologne, Germany.
authors.forename: Lebriz
authors.initials: L
authors.lastname: Altay
authors.affiliation: University Hospital of Cologne, Department of Ophthalmology, Cologne, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Schick
authors.affiliation: Leiden University Medical Center, Department of Nephrology, Leiden, The Netherlands.
authors.forename: Mohamed R
authors.initials: MR
authors.lastname: Daha
authors.affiliation: University Hospital of Cologne, Department of Ophthalmology, Cologne, Germany.
authors.forename: Sascha
authors.initials: S
authors.lastname: Fauser
authors.affiliation: Radboud university medical center, Department of Ophthalmology, Nijmegen, The Netherlands.
authors.forename: Carel B
authors.initials: CB
authors.lastname: Hoyng
authors.affiliation: Radboud university medical center, Department of Ophthalmology, Nijmegen, The Netherlands.|Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.|Radboud university medical center, Department of Human Genetics, Nijmegen, The Netherlands.
authors.forename: Anneke I
authors.initials: AI
authors.lastname: den Hollander
authors.affiliation: Radboud university medical center, Department of Ophthalmology, Nijmegen, The Netherlands.|Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
authors.forename: Eiko K
authors.initials: EK
authors.lastname: de Jong
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003167:Complement Activation; D011415:Complement Factor B / Q000235:genetics*; D017242:Complement Factor H / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: C493495:CFH protein, human; D017242:Complement Factor H; D011415:Complement Factor B