Variation of codons 1961 and 2177 of the Stargardt disease gene is not associated with age-related macular degeneration

Détails

ID Serval
serval:BIB_B78772500126
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Variation of codons 1961 and 2177 of the Stargardt disease gene is not associated with age-related macular degeneration
Périodique
Archives of Ophthalmology
Auteur⸱e⸱s
Guymer  R. H., Heon  E., Lotery  A. J., Munier  F. L., Schorderet  D. F., Baird  P. N., McNeil  R. J., Haines  H., Sheffield  V. C., Stone  E. M.
ISSN
0003-9950 (Print)
Statut éditorial
Publié
Date de publication
05/2001
Volume
119
Numéro
5
Pages
745-51
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: May
Résumé
OBJECTIVES: To investigate the role of 2 specific alleles of the Stargardt disease gene (ABCA4) in the pathogenesis of age-related macular degeneration (AMD). Secondary objectives were to investigate differences in frequency of the G1961E allele in selected ethnic groups as well as to examine the segregation of both G1961E and D2177N alleles in 5 multiplex families with AMD. METHODS: Five hundred forty-four patients with AMD and 689 controls were ascertained from 3 continents. Blood samples from 62 normal individuals of Somalian ancestry were also obtained. Participants were screened for the presence of these ABCA4 alleles with a combination of restriction digestion and single-strand conformation polymorphism analysis of polymerase chain reaction amplification products. Detected alleles were confirmed by DNA sequencing. The number of subjects exhibiting the G1961E or D2177N variants were compared between AMD and control groups using a 2-tailed Fisher exact test. RESULTS: There was no significant difference (P >.1) in the frequency of the G1961E and D2177N alleles in patients with AMD (2.2%) vs controls (1.0%). In contrast, there was a significant difference (P< .001) in the frequency of the G1961E alleles between normal individuals of Somali ancestry (11.3%) and normal individuals from other populations (0.4%). There was no evidence of cosegregation of these alleles and the AMD phenotype in the 5 multiplex families with AMD examined. These two ABCA4 alleles were slightly more frequent in patients with AMD with choroidal neovascularization (2.7%) than those without this complication (2.5%). CONCLUSIONS: Somali ancestry is more than 100 times more strongly associated with presence of the G1961E allele than the AMD phenotype. This study did not find any statistically significant evidence for involvement of the G1961E or D2177N alleles of the ABCA4 gene in AMD. CLINICAL RELEVANCE: The ABCA4 gene is definitively involved in the pathogenesis of Stargardt disease and some cases of photoreceptor degeneration. However, it does not seem to be involved in a statistically significant fraction of AMD cases.
Mots-clé
ATP-Binding Cassette Transporters/*genetics Adult Aged Aged, 80 and over Alleles Codon/*genetics DNA Mutational Analysis Female Humans Macular Degeneration/diagnosis/*genetics Male Middle Aged Pedigree Polymorphism, Single-Stranded Conformational Rod Outer Segments/pathology *Variation (Genetics)
Pubmed
Web of science
Création de la notice
28/01/2008 12:59
Dernière modification de la notice
20/08/2019 15:25
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