title: HTRA1 promoter polymorphism in wet age-related macular degeneration.
abstract: 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.
authors.affiliation: Department of Epidemiology and Public Health, Yale University, 60 College Street, New Haven, CT 06520, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Dewan
authors.forename: Mugen
authors.initials: M
authors.lastname: Liu
authors.forename: Stephen
authors.initials: S
authors.lastname: Hartman
authors.forename: Samuel Shao-Min
authors.initials: SS
authors.lastname: Zhang
authors.forename: David T L
authors.initials: DT
authors.lastname: Liu
authors.forename: Connie
authors.initials: C
authors.lastname: Zhao
authors.forename: Pancy O S
authors.initials: PO
authors.lastname: Tam
authors.forename: Wai Man
authors.initials: WM
authors.lastname: Chan
authors.forename: Dennis S C
authors.initials: DS
authors.lastname: Lam
authors.forename: Michael
authors.initials: M
authors.lastname: Snyder
authors.forename: Colin
authors.initials: C
authors.lastname: Barnstable
authors.forename: Chi Pui
authors.initials: CP
authors.lastname: Pang
authors.forename: Josephine
authors.initials: J
authors.lastname: Hoh
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D044466:Asian People / Q000235:genetics; D047369:Chromatin Immunoprecipitation; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006367:HeLa Cells; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D015810:Linkage Disequilibrium; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D015861:Retinal Neovascularization; D012697:Serine Endopeptidases / Q000235:genetics*; D026362:Serum Response Factor / Q000378:metabolism; D050656:Transcription Factor AP-2 / Q000378:metabolism
chemical_list: D026362:Serum Response Factor; D050656:Transcription Factor AP-2; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases