, 36:9627 | Cite as

In-depth analyses unveil the association and possible functional involvement of novel RAD51B polymorphisms in age-related macular degeneration

  • Xi K. Chu
  • Catherine B. Meyerle
  • Xiaoling Liang
  • Emily Y. Chew
  • Chi-Chao Chan
  • Jingsheng Tuo


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.


Age-related macular degeneration RAD51B DNA repair Single-nucleotide polymorphism Functional genomicsl Gene expression 



The authors thank Angel Garced, R.N., Katherine Shimel, R.N., and Sun–min Ro, R.N. for their assistance in contacting study participants and collecting blood samples; Arvydas Maminishkis, Ph.D. for providing fhRPE cells. We also thank the study participants and their families for enrolling in this study. This research was supported by “The Intramural Research Program of the National Eye Institute, NIH,” the “Specialized Research Foundation for Doctoral Program of Higher Education in China (20120171110086),” and the “Science and Technology Planning Project of Guangzhou City (11C22060787) of China.”

Conflict of interest



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Copyright information

© American Aging Association 2014

Authors and Affiliations

  • Xi K. Chu
    • 1
  • Catherine B. Meyerle
    • 2
  • Xiaoling Liang
    • 3
  • Emily Y. Chew
    • 2
  • Chi-Chao Chan
    • 1
  • Jingsheng Tuo
    • 1
  1. 1.Laboratory of Immunology, National Eye InstituteNational Institutes of HealthBethesdaUSA
  2. 2.Division of Epidemiology and Clinical Applications, National Eye InstituteNational Institutes of HealthBethesdaUSA
  3. 3.State Key Laboratory of OphthalmologyZhongshan Ophthalmic CenterGuangzhouChina

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