Genetic linkage analysis of the TIMP3 locus in age-related macular degeneration

J. M. Seddon, M. Pericak-Vance, J. Haines, J. Rimmler, H. A. De La Paz

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1 Scopus citations


Purpose. Age-related macular degeneration (ARMD) is a genetically complex disorder. Tissue inhibitor of metalloproteinases-3 (TIMP3) on chromosome 22 has been identified as the gene that is mutated in Sorsby's fundus dystrophy, a hereditary macular dystrophy which phenotypically resembles ARMD. The purpose of this study was to determine whether TIMP3 is associated with ARMD. Methods. 37 multiplex ARMD families as well as 30 sporadic cases were identified in Massachusetts and North Carolina. The macular findings were graded according to a modification of the grading system used in the Age-Related Eye Disease Study (AREDS), and individuals with extensive intermediate drusen, any large drusen, geographic atrophy, or evidence of exudative maculopathy were coded as affected for the purpose of the analysis. Linkage analysis was performed using both model dependent [LOD score] and model independent [sibpair and APM] methods. Two markers, D22S280 and D22S529, tightly linked to TIMP3, were chosen for the analysis. Association studies were performed using standard methodology comparing the ARMD patients with a series of age, sex and ethnically matched controls. Results. LOD score analysis excluded linkage in these data for approximately 10cM around TIMP3. In addition no significant findings were observed with either the sibpair or APM analyses. Association studies using a series of age-matched controls also failed to generate significant results. Conclusions. No evidence for linkage or association was found between ARMD and TIMP3. These data suggest that although clinically similar, the genetic variation found in these 2 disorders are of different etiologies.

Original languageEnglish (US)
Pages (from-to)S992
JournalInvestigative Ophthalmology and Visual Science
Issue number3
StatePublished - Feb 15 1996
Externally publishedYes

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


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