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

Objectives: To investigate the role of 2 specific alleles of the Stargardt disease gene (ABCA4) in the pathogenesis of age-related macular degeneratio n (AMD). Secondary objectives were to investigate differences in frequency of the G1961E allele in selected ethnic groups as well as to examine the se gregation of both G1961E and D2177N alleles in 5 multiplex families with AM D. Methods: Five hundred forty-four patients with AMD and 689 controls were as certained from 3 continents. Blood samples from 62 normal individuals of So malian ancestry were also obtained. Participants were screened for the pres ence of these ABCA4 alleles with a combination of restriction digestion and single-strand conformation polymorphism analysis of polymerase chain react ion amplification products. Detected alleles were confirmed by DNA sequenci ng. The number of subjects exhibiting the G1961E or D2177N variants were co mpared 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 o f 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 fre quent in patients with AMD with choroidal neovascularization (2.7%) than th ose without this complication (2.5%). Conclusions: Somali ancestry is more than 100 times more strongly associate d with presence of the G1961E allele than the AMD phenotype. This study did not find any statistically significant evidence for involvement of the G19 61E or D2177N alleles of the ABCA4 gene in AMD. Clinical Relevance: The ABCA4 gene is definitively involved in the pathogen esis of Stargardt disease and some cases of photoreceptor degeneration. How ever, it does not seem to be involved in a statistically significant fracti on of AMD cases.