Human Molecular Genetics Advance Access originally published online on August 11, 2006
Human Molecular Genetics 2006 15(18):2784-2790; doi:10.1093/hmg/ddl220
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Systematic review and meta-analysis of the association between complementary factor H Y402H polymorphisms and age-related macular degeneration
1 Centre for Clinical Epidemiology and Biostatistics and 2 Clinical Pharmacology Unit, School of Medical Practice and Population Health, University of Newcastle, Newcastle, NSW, Australia, 3 Clinical Epidemiology Unit, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand, 4 Department of Epidemiology and Public Health, Yale University School of Medicine, USA, 5 deCODE Genetics Inc., Reykjavik, Iceland and 6 Eccles Institute of Human Genetics, University of Utah, Salt Lake City, UT, USA
* To whom correspondence should be addressed at: Centre for Clinical Epidemiology and Biostatistics, University of Newcastle, Newcastle, NSW 2300, Australia. Tel: +66 61249236857; Fax: +66 61249236148; Email: ammarin.thakkinstian{at}newcastle.edu.au
Received April 23, 2006; Accepted August 3, 2006
Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world and complement factor H (CFH) polymorphism has been found to associated with the AMD. We performed a meta-analysis to estimate the magnitude of the gene effect and the possible mode of action. A meta-analysis of eight studies assessing association between the CFH Y402H polymorphism and AMD was performed. Data extraction and study quality assessment were performed in duplicate, and heterogeneity and publication bias were explored. There was strong evidence for association between CFH and AMD, with those having CC and TC genotypes being roughly six and 2.5 times more likely to have AMD than patients with TT genotype, suggesting a co-dominant, multiplicative genetic model. The population attributable risk for the CC/TC genotype is 58.9%, i.e. the CFH polymorphism is involved in over half of all AMD. This meta-analysis summarizes the strong evidence for an association between CFH and AMD and indicates a multiplicative model with each C allele increasing the odds of AMD by 
2.5-fold. This result is at least as important at the population level as ApoE4 and Alzheimer's disease, playing a role in almost 60% of AMD at the population level.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L. Bertram Genetic Research in Schizophrenia: New Tools and Future Perspectives Schizophr Bull, September 1, 2008; 34(5): 806 - 812. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. K. Ng, L. J. Chen, D. T. L. Liu, P. O. S. Tam, W. M. Chan, K. Liu, Y. J. Hu, K. K. L. Chong, C. S. L. Lau, S. W. Y. Chiang, et al. Multiple Gene Polymorphisms in the Complement Factor H Gene Are Associated with Exudative Age-Related Macular Degeneration in Chinese Invest. Ophthalmol. Vis. Sci., August 1, 2008; 49(8): 3312 - 3317. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Ormsby, S. Ranganathan, J. C. Tong, K. M. Griggs, D. P. Dimasi, A. W. Hewitt, K. P. Burdon, J. E. Craig, J. Hoh, and D. L. Gordon Functional and Structural Implications of the Complement Factor H Y402H Polymorphism Associated with Age-Related Macular Degeneration Invest. Ophthalmol. Vis. Sci., May 1, 2008; 49(5): 1763 - 1770. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I Droz, I Mantel, A Ambresin, M Faouzi, D F Schorderet, and F L Munier Genotype-phenotype correlation of age-related macular degeneration: influence of complement factor H polymorphism Br. J. Ophthalmol., April 1, 2008; 92(4): 513 - 517. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Melzer, S. Hogarth, K. Liddell, T. Ling, S. Sanderson, and R. L Zimmern Genetic tests for common diseases: new insights, old concerns BMJ, March 15, 2008; 336(7644): 590 - 593. [Full Text] [PDF]
|
|
|
|
 |
|
 C. Minelli, J. R Thompson, K. R Abrams, A. Thakkinstian, and J. Attia How should we use information about HWE in the meta-analyses of genetic association studies? Int. J. Epidemiol., February 1, 2008; 37(1): 136 - 146. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Coffey, C. Gias, C. J. McDermott, P. Lundh, M. C. Pickering, C. Sethi, A. Bird, F. W. Fitzke, A. Maass, L. L. Chen, et al. Complement factor H deficiency in aged mice causes retinal abnormalities and visual dysfunction PNAS, October 16, 2007; 104(42): 16651 - 16656. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Swaroop, K. E. Branham, W. Chen, and G. Abecasis Genetic susceptibility to age-related macular degeneration: a paradigm for dissecting complex disease traits Hum. Mol. Genet., October 15, 2007; 16(R2): R174 - R182. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Spencer, M. A. Hauser, L. M. Olson, N. Schnetz-Boutaud, W. K. Scott, S. Schmidt, P. Gallins, A. Agarwal, E. A. Postel, M. A. Pericak-Vance, et al. Haplotypes Spanning the Complement Factor H Gene Are Protective against Age-Related Macular Degeneration Invest. Ophthalmol. Vis. Sci., September 1, 2007; 48(9): 4277 - 4283. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. P. Herbert, J. A. Deakin, C. Q. Schmidt, B. S. Blaum, C. Egan, V. P. Ferreira, M. K. Pangburn, M. Lyon, D. Uhrin, and P. N. Barlow Structure Shows That a Glycosaminoglycan and Protein Recognition Site in Factor H Is Perturbed by Age-related Macular Degeneration-linked Single Nucleotide Polymorphism J. Biol. Chem., June 29, 2007; 282(26): 18960 - 18968. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. DeWan, M. Liu, S. Hartman, S. S.-M. Zhang, D. T. L. Liu, C. Zhao, P. O. S. Tam, W. M. Chan, D. S. C. Lam, M. Snyder, et al. HTRA1 Promoter Polymorphism in Wet Age-Related Macular Degeneration Science, November 10, 2006; 314(5801): 989 - 992. [Abstract] [Full Text] [PDF]
|
|