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Published Online October 19, 2006
Science DOI: 10.1126/science.1133807

Reports

Submitted on August 14, 2006
Accepted on October 5, 2006

HTRA1 Promoter Polymorphism in Wet Age-Related Macular Degeneration

Andrew DeWan 1, Mugen Liu 2, Stephen Hartman 3, Shaomin Zhang 2, David T. L. Liu 4, Connie Zhao 5, Pancy O. S. Tam 4, Wai Man Chan 4, Dennis S. C. Lam 4, Michael Snyder 3, Colin Barnstable 2, Chi Pui Pang 4, Josephine Hoh 6*

1 Department of Epidemiology and Public Health, Yale University, 60 College Street, New Haven, CT 06520, USA.
2 Department of Ophthalmology and Visual Science, Yale University, 330 Cedar Street, New Haven, CT 06520, USA.
3 Department of Molecular, Cellular, and Developmental Biology, Yale University, 219 Prospect Street, New Haven, CT 06520, USA.
4 Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
5 Genomics Resource Center, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
6 Department of Epidemiology and Public Health, Yale University, 60 College Street, New Haven, CT 06520, USA; Department of Ophthalmology and Visual Science, Yale University, 330 Cedar Street, New Haven, CT 06520, USA.

* To whom correspondence should be addressed.
Josephine Hoh , E-mail: josephine.hoh{at}yale.edu

Age-related macular degeneration (AMD), the most common cause of irreversible vision loss in individuals aged older than 50 years, is classified as either wet (neovascular) or dry (nonneovascular). Inherited variation in the complement factor H gene is a major risk factor for drusen in dry AMD. Here we report that a single nucleotide polymorphism in the promoter region of HTRA1, a serine protease gene on chromosome 10q26, is a major genetic risk factor for wet AMD. A whole-genome association mapping strategy was applied to a Chinese population, yielding a P value of <10-11. Individuals with the risk-associated genotype were estimated to have a likelihood of developing wet AMD 10 times that of individuals with the wild-type genotype.


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