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Gaofeng Wang, Sander R Dubovy, Stephen G Schwartz, Jaclyn L Kovach, Anita Agarwal, William K Scott, Jonathan Haines, Margaret A Pericak-Vance; Genotype at polymorphism rs5749482 and TIMP3 expression in AMD. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2221.
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To analyze the relationship between an age-related macular degeneration (AMD) associated variant in the TIMP3 gene and its transcription in human retinas and peripheral blood.
RNAs were extracted from tissues containing retina-RPE-choroid of 92 unrelated Caucasian subjects without any known eye diseases and peripheral white blood cells of another 94 individuals with different AMD stages as determined by a modified AREDS grading system (N=33 for Grade 1; 8 for Grade 2; 13 for Grade 3; 17 for Grade 4 and 23 for Grade 5). Genotypes at TIMP3 variant rs5749482 were obtained by a Taqman assay. Quantitative RT-PCR was applied to measure TIMP3 mRNA in retina-RPE-choroid and blood samples.
No significant difference (P < 0.05) in the TIMP3 mRNA level was found between the different genotypes at rs5749482 or between AMD patients (combined or individual Grades 3, 4, 5) and controls (Grades 1, 2) in peripheral white blood cells. In contrast, risk genotype CC was associated with a lower level of TIMP3 mRNA (P < 0.05) in retina-RPE-choroid tissues.
These results suggest that an increased risk of AMD conferred by polymorphism rs5749482 could possibly be mediated by tissue-specific down-regulated transcription of TIMP3 in the retina. Further studies are warranted to verify the functional association between SNP rs5749482 and TIMP3 transcription in AMD.
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