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ObjectiveTo investigate the association between variants in the complement component 5 (C5) gene and age-related macular degeneration (AMD).DesignSeparate and combined data from 3 large AMD case-control studies and a prospective population-based study (The Rotterdam Study).ParticipantsA total of 2599 AMD cases and 3458 ethnically matched controls.MethodsFifteen single nucleotide polymorphisms (SNPs) spanning the C5 gene were initially genotyped in 375 cases and 199 controls from The Netherlands (The Amsterdam/Rotterdam-Netherlands [AMRO-NL] study population). Replication testing of selected SNPs was performed in the Rotterdam Study (NL) and study populations from Southampton, United Kingdom (UK), and New York, United States (US).Main outcome measuresEarly and late stages of prevalent and incident AMD, graded according to (a modification of) the international grading and classification system of AMD.ResultsSignificant allelic or genotypic associations between 8 C5 SNPs and AMD were found in the AMRO-NL study and this risk seemed to be independent of CFH Y402H, LOC387715 A69S, age, and gender. None of these findings could be confirmed consistently in 3 replication populations.ConclusionsAlthough the complement pathway, including C5, plays a crucial role in AMD, and the C5 protein is present in drusen, no consistent significant associations between C5 SNPs and AMD were found in any of these studies. The implications for genetic screening of AMD are discussed.

Original publication




Journal article



Publication Date





500 - 511


Department of Clinical and Molecular Ophthalmogenetics, The Netherlands Institute for Neuroscience, an institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, The Netherlands.


Humans, Macular Degeneration, Case-Control Studies, Prospective Studies, Genotype, Polymorphism, Single Nucleotide, Aged, Complement C5, Female, Male