HTRA1 promoter polymorphism in wet age-related macular degeneration

Science. 2006 Nov 10;314(5801):989-92. doi: 10.1126/science.1133807. Epub 2006 Oct 19.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging
  • Asian Continental Ancestry Group / genetics
  • Chromatin Immunoprecipitation
  • Chromosomes, Human, Pair 10 / genetics
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • HeLa Cells
  • High-Temperature Requirement A Serine Peptidase 1
  • Humans
  • Linkage Disequilibrium
  • Macular Degeneration / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Promoter Regions, Genetic*
  • Retinal Neovascularization
  • Serine Endopeptidases / genetics*
  • Serum Response Factor / metabolism
  • Transcription Factor AP-2 / metabolism

Substances

  • Serum Response Factor
  • Transcription Factor AP-2
  • High-Temperature Requirement A Serine Peptidase 1
  • HtrA1 protein, human
  • Serine Endopeptidases