The complement component 5 gene and age-related macular degeneration.
OBJECTIVE
To investigate the association between variants in the complement component 5 (C5) gene and age-related macular degeneration (AMD).


METHODS
Separate and combined data from 3 large AMD case-control studies and a prospective population-based study (The Rotterdam Study).


METHODS
A total of 2599 AMD cases and 3458 ethnically matched controls.


METHODS
Fifteen 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).


METHODS
Early and late stages of prevalent and incident AMD, graded according to (a modification of) the international grading and classification system of AMD.


RESULTS
Significant 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.


CONCLUSIONS
Although 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.
Baas
Dominique C
DC
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.
Ho
Lintje
L
Ennis
Sarah
S
Merriam
Joanna E
JE
Tanck
Michael W T
MW
Uitterlinden
André G
AG
de Jong
Paulus T V M
PT
Cree
Angela J
AJ
Griffiths
Helen L
HL
Rivadeneira
Fernando
F
Hofman
Albert
A
van Duijn
Cornelia
C
Smith
R Theodore
RT
Barile
Gaetano R
GR
Gorgels
Theo G M F
TG
Vingerling
Johannes R
JR
Klaver
Caroline C W
CC
Lotery
Andrew J
AJ
Allikmets
Rando
R
Bergen
Arthur A B
AA
D000368:Aged; D016022:Case-Control Studies; D003182:Complement C5 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies
D003182:Complement C5