Toll‐like receptor 3 C1234T may protect against geographic atrophy through decreased dsRNA binding capacity

ABSTRACT The genetic association between a variant in the Toll‐like receptor 3 (TLR3) gene (C1234T in mRNA, L412F in protein, Reference SNP Cluster Report rs3775291) and geographic atrophy (GA; also called advanced “dry” age‐related macular degeneration) was controversial in previous studies. We per...

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Bibliographic Details
Published in:The FASEB journal 2011-10, Vol.25 (10), p.3489-3495
Main Authors: Zhou, Peng, Fan, Lei, Yu, Ke‐Da, Zhao, Ming‐Wei, Li, Xiao‐Xin
Format: Article
Language:English
Subjects:
age‐related macular degeneration
double‐stranded RNA
Gene Expression Regulation - physiology
Genetic Predisposition to Disease
Geographic Atrophy - genetics
Humans
Odds Ratio
Polymorphism, Single Nucleotide
Risk Factors
RNA, Double-Stranded - genetics
RNA, Double-Stranded - metabolism
Toll-Like Receptor 3 - genetics
Toll-Like Receptor 3 - metabolism
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Summary:ABSTRACT The genetic association between a variant in the Toll‐like receptor 3 (TLR3) gene (C1234T in mRNA, L412F in protein, Reference SNP Cluster Report rs3775291) and geographic atrophy (GA; also called advanced “dry” age‐related macular degeneration) was controversial in previous studies. We performed a meta‐analysis by pooling the current evidence in literature and found that the T allele of the TLR3 C1234T variant showed a summary odds ratio of 0.753 (95% confidence interval: 0.612‐0.927; P=0.007). Further experiments were performed to analyze how this mutant influences the function of TLR3. We found that this SNP did not affect mRNA, protein, or surface expression of TLR3. However, the binding capacity of L412F mutation of TLR3 for double‐stranded RNA in the TLR3 protein was only 51.12 ± 3.96% (P
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.11-189258