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Exclusion of TIMP3 as a candidate locus in age-related macular degeneration.

Publication ,  Journal Article
De La Paz, MA; Pericak-Vance, MA; Lennon, F; Haines, JL; Seddon, JM
Published in: Invest Ophthalmol Vis Sci
May 1997

PURPOSE: Age-related macular degeneration (AMD) is a genetically complex disorder. Tissue inhibitor of metalloproteinases-3 (TIMP3) on chromosome 22 has been identified as a gene that is mutated in Sosby's fundus dystrophy, an autosomal-dominant macular dystrophy that phenotypically resembles AMD. The purpose of this study was to determine whether TIMP3 is a major susceptibility gene for the AMD phenotype. METHODS: Thirty-eight multiplex families with AMD 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, and persons 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) methods. For the lod score analysis, both autosomal-dominant as well as recessive low penetrance "affecteds only" analyses were examined. Three markers, D22S280, D22S529, and D225268, linked tightly and flanking the TIMP3 locus, were chosen for the analysis. Association studies were performed by examining one randomly chosen affected person per family and comparing the patients with AMD with a series of age, gender, and ethnically matched control subjects with no known history of AMD. RESULTS: Lod score analysis excluded linkage in these data for an approximately 10-cm interval surrounding the TIMP3 gene for all models tested. In addition, no significant findings were observed with either the sibpair or the association study. CONCLUSIONS: No evidence of linkage or association or both was found between AMD and TIMP3 in these 38 families. These data suggest that although clinically similar, the genetic defect in Sorsby's fundus dystrophy is of a different cause than the majority of the genetic causes of AMD.

Duke Scholars

Published In

Invest Ophthalmol Vis Sci

ISSN

0146-0404

Publication Date

May 1997

Volume

38

Issue

6

Start / End Page

1060 / 1065

Location

United States

Related Subject Headings

  • Tissue Inhibitor of Metalloproteinase-3
  • Proteins
  • Pedigree
  • Ophthalmology & Optometry
  • Macular Degeneration
  • Lod Score
  • Humans
  • Haplotypes
  • Genetic Linkage
  • Chromosome Mapping
 

Citation

APA
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ICMJE
MLA
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De La Paz, M. A., Pericak-Vance, M. A., Lennon, F., Haines, J. L., & Seddon, J. M. (1997). Exclusion of TIMP3 as a candidate locus in age-related macular degeneration. Invest Ophthalmol Vis Sci, 38(6), 1060–1065.
De La Paz, M. A., M. A. Pericak-Vance, F. Lennon, J. L. Haines, and J. M. Seddon. “Exclusion of TIMP3 as a candidate locus in age-related macular degeneration.Invest Ophthalmol Vis Sci 38, no. 6 (May 1997): 1060–65.
De La Paz MA, Pericak-Vance MA, Lennon F, Haines JL, Seddon JM. Exclusion of TIMP3 as a candidate locus in age-related macular degeneration. Invest Ophthalmol Vis Sci. 1997 May;38(6):1060–5.
De La Paz, M. A., et al. “Exclusion of TIMP3 as a candidate locus in age-related macular degeneration.Invest Ophthalmol Vis Sci, vol. 38, no. 6, May 1997, pp. 1060–65.
De La Paz MA, Pericak-Vance MA, Lennon F, Haines JL, Seddon JM. Exclusion of TIMP3 as a candidate locus in age-related macular degeneration. Invest Ophthalmol Vis Sci. 1997 May;38(6):1060–1065.

Published In

Invest Ophthalmol Vis Sci

ISSN

0146-0404

Publication Date

May 1997

Volume

38

Issue

6

Start / End Page

1060 / 1065

Location

United States

Related Subject Headings

  • Tissue Inhibitor of Metalloproteinase-3
  • Proteins
  • Pedigree
  • Ophthalmology & Optometry
  • Macular Degeneration
  • Lod Score
  • Humans
  • Haplotypes
  • Genetic Linkage
  • Chromosome Mapping