Document Detail


Influence of TIMP3/SYN3 polymorphisms on the phenotypic presentation of age-related macular degeneration.
MedLine Citation:
PMID:  23422939     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Age-related macular degeneration (AMD) is a leading cause of irreversible central visual loss in the elderly. A recent genome-wide association studies (GWAS) reported that rs9621532 near the tissue inhibitor of metalloproteinase 3 (TIMP3)/synapsin III (SYN3) region of 22q12.3 is associated with AMD. In this study, we characterize its phenotypic influence on AMD using three independent study cohorts: case-control studies from the National Eye Institute Clinical Center (NEI, n=397) and the Age-Related Eye Disease Study (n=523) as well as a nested case-control study from Blue Mountains Eye Study (BMES, n=852). Comparisons between cases and controls show no association between rs9621532 and AMD in the three sample sets. However, stratifying NEI cases uncovers a moderate protective role of rs9621532 in neovascular AMD (nAMD) and the association adhered to a dominant model (odds ratios=0.32; 95% CI: 0.11-0.89; P=0.02). The BMES data followed the same pattern of association with nAMD as that seen in the NEI sample but did not reach statistical significance. Polychotomous logistic regression showed a trend that rs9621532 correlates with less severe disease, for example, with the majority of carriers having intermediate AMD rather than nAMD/geographic atrophy AMD. Functionally, rs9621532 influences TIMP3 mRNA expression in cultured primary human fetal retinal pigment epithelium (hfRPE) cells. In hfRPE donors carrying the protective rs9625132 allele, we measured a reduction in TIMP3 mRNA by quantitative RT-PCR. Our data suggest that rs9621532 carriers have a lower risk of developing nAMD, potentially because of decreased transcription of TIMP3.European Journal of Human Genetics advance online publication, 20 February 2013; doi:10.1038/ejhg.2013.14.
Authors:
Daniel Ardeljan; Catherine B Meyerle; Elvira Agron; Jie Jin Wang; Paul Mitchell; Emily Y Chew; Jing Zhao; Arvydas Maminishkis; Chi-Chao Chan; Jingsheng Tuo
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-2-20
Journal Detail:
Title:  European journal of human genetics : EJHG     Volume:  -     ISSN:  1476-5438     ISO Abbreviation:  Eur. J. Hum. Genet.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-2-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9302235     Medline TA:  Eur J Hum Genet     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
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