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Influence of TIMP3/SYN3 polymorphisms on the phenotypic presentation of Age-Related Macular Degeneration

Thursday, October 11, 2012 — Poster Session III

10:00 a.m. – Noon

Natcher Conference Center, Building 45




  • J Tuo
  • D Ardeljan
  • C Meyerle
  • E Agron
  • JJ Wang
  • P Mitchell
  • EY Chew
  • J Zhao
  • A Maminishkis
  • SS Miller
  • CC Chan


A large-scale GWAS reported several additional age-related macular degeneration (AMD) susceptibility loci, one of which is rs9621532 near the TIMP3/SYN3. We used 2 case-control studies (NEI, AREDS) and a nested case-control study (BMES) to further characterize the phenotypic influence of the SNP on AMD. To test the functional involvement of the SNP in the regulation of gene expression, TIMP3 and SYN3 transcripts were evaluated by qRT-PCR using human fetal retinal pigment epithelium cells. The results show no association between rs9621532 and AMD as a whole in the 3 sample sets, respectively. However, stratification of NEI cases uncovered a moderate protective role of rs9621532 in neovascular AMD (nAMD) (OR=0.32; P =0.02) and the association adhered to a dominant model. The BMES rs9621532 data followed the same pattern with nAMD association as that seen in the NEI sample set but did not reach significance. Polychotomous logistic regression shows a trend that rs9621532 correlates with milder disease. TIMP3 and SYN3 mRNA expression is higher in hfRPE homozygous for the major rs9621532 allele than in heterozygotes. Our data suggest that rs9621532 carriers have a lower risk of developing exudative AMD and the SNP might be functionally involved in the regulation of TIMP3/SYN3 expression.

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