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| Content Provider | PubMed Central |
|---|---|
| Author | Chu, Xi K. Meyerle, Catherine B. Liang, Xiaoling Chew, Emily Y. Chan, Chi-chao Tuo, Jingsheng |
| Abstract | The contribution of DNA damage to the pathogenesis of age-related macular degeneration (AMD) has been reported. Recently, a genomewide association study detected the association of a single-nucleotide polymorphism (SNP) in RAD51B (rs8017304 A>G) with AMD. RAD51B is involved in recombinational repair of DNA double-strand breaks. We analyzed RAD51B influence on AMD using two cohorts from Caucasian and Han Chinese populations. The Caucasian set replicated the rs8017304 A>G association and revealed two novel AMD-associated SNPs in RAD51B, rs17105278 T>C and rs4902566 C>T. Under the dominant model, these two SNPs exhibit highly significant disease risk. SNP–SNP interaction analysis on rs17105278 T>C and rs4902566 C>T homozygous demonstrated a synergistic effect on AMD risk, reaching an odds ratio multifold higher than well-established AMD susceptibility loci in genes such as CFH, HTRA1, and ARMS2. Functional study revealed lower RAD51B mRNA expression in cultured primary human fetal retinal pigment epithelium (hfRPE) carrying rs17105278 T>C variants than in hfRPE carrying rs17105278 wild type. We concluded that the risk of developing AMD exhibits dose dependency as well as an epistatic combined effect in rs17105278 T>C and rs4902566 C>T carriers and that the elevated risk for rs17105278 T>C carriers may be due to decreased transcription of RAD51B. This study further confirms the role of DNA damage/DNA repair in AMD pathogenesis. |
| Related Links | http://dx.doi.org/10.1007/s11357-014-9627-2 |
| Starting Page | 9627 |
| File Format | |
| ISSN | 15744647 |
| e-ISSN | 15744647 |
| Journal | Age |
| Issue Number | 3 |
| Volume Number | 36 |
| Language | English |
| Publisher | Springer Netherlands |
| Publisher Date | 2014-06-01 |
| Access Restriction | Open |
| Rights Holder | Springer Netherlands |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Aging Geriatrics and Gerontology |
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