Toll-like receptor polymorphisms and age-related macular degeneration: replication in three case-control samples.
OBJECTIVE
Innate immunity appears to play a key role in age-related macular degeneration (AMD). Although two previous studies reported that gene variations in Toll-like receptor (TLR)-3 and -4 are associated with AMD, other studies have not confirmed these associations. In this study, three independent samples (two U.S. clinic-based case-control study samples and one Australian population-based study sample) were used to further assess the association of the polymorphisms rs3775291 in TLR3 and rs4986790 in TLR4 with AMD.


METHODS
AMD cases and unrelated controls were collected from the National Eye Institute Clinical Center (NEI, n = 320), the Age-Related Eye Disease Study (AREDS, n = 483), and the Blue Mountains Eye Study (BMES, n = 852). DNA extracted from subjects was genotyped for rs3775291 and rs4986790, and the associations with AMD were investigated.


RESULTS
Neither of the two polymorphisms rs3775291 and rs4986790 had a statistically significant association with AMD in any of the three sample sets or in combinations of the sets. Analysis of the combined geographic atrophy or neovascular AMD cases in the NEI, AREDS, and BMES sample sets also failed to demonstrate statistically significant associations of those two single nucleotide polymorphisms with advanced AMD.


CONCLUSIONS
Even with previously verified samples sets and adequate study powers, the results did not confirm the reported associations of TLR3 rs3775291 and TLR4 rs4986790 with AMD in the three independent samples, individually or combined.
Cho
Youngeun
Y
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-1857, USA.
Wang
Jie Jin
JJ
Chew
Emily Y
EY
Ferris
Frederick L
FL
Mitchell
Paul
P
Chan
Chi-Chao
CC
Tuo
Jingsheng
J
D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D051196:Toll-Like Receptor 3 / Q000235:genetics*; D051197:Toll-Like Receptor 4 / Q000235:genetics*
C495344:TLR3 protein, human; C495345:TLR4 protein, human; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4