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KP Magnusson, H Sigurdsson, S Smarason, A Björnsdottir, H Petursson, G Helgadottir, F Jonassson, E Stefansson, K StefanssonAMD Genetics Research Group; Genetic association of Apolipoprotein E with severe exudative Age-related macular degeneration (AMD) . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1843.
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Purpose: ApoE-ϵ4 allele has been reported to be associated with a decreased risk for AMD. We have previously demonstrated a familial pattern in AMD in Iceland. The aim of this study is to determine if there is an association between ApoE and developing any of the three major forms of AMD, Early AMD, geographic atrophy or severe exudative (disciform) degeneration. Method: ApoE genotyping was performed by mass spectrometry, accomplished by measuring the products of an allele specific mini-sequencing reaction. The general protocol was: PCR, Exo/SAP cleanup and mini-sequencing reaction. The final products where desalted prior to analysis using Multiscreen 384® SNP (Millipore) cleanup plates. The desalted products were spotted onto a 400µm Anchortarget (Bruker) along with 3-hydroxypicolinic acid (3-HPA) as matrix and analyzed using a ReflexIII (Bruker) operated in the linear mode. The products for both ApoE SNPs were produced and analyzed simultaneously. Genotyping was performed on a total of 1253 individuals, 708 AMD patients and 545 healthy relatives. The patients group consisted of 320 individuals with Early AMD, 202 with Geographic atrophy and 212 with exudative AMD, where of 58 had both Geographic atrophy and exudative AMD. Both eyes were analyzed, photographed and classified according to international classification and grading system. The two patients groups and the control group, that are described in results are; exudative AMD with geographic atrophy (N=142), exudative without geographic atrophy (N=86) and control group (N=313). The individuals in these groups are unrelated in ≷6meiosis. Results: There was a significant difference in allelic distribution of the ApoE locus for both exudative AMD groups, with or without geographic atrophy (p-values <0.001 in both cases) characterised by a marked decrease of the ϵ4 alle. A significantly lower frequency of the ApoE-ϵ3/ϵ4 genotype was observed when the two exudative AMD groups were compared with the control group, odds ratio (OR) 0.357 (CI 0.195-0.654) and OR 0.034 (CI 0.005-0.253), respectively. Statistical analysis on the ϵ4/ϵ4 genotype was limited due to low sample number. The ApoE polymorphism did not show a significant association with Early AMD or geographic atrophy. Conclusion: This study provides evidence for a protective effect of the ApoE-ϵ4 allele in the etiology of the severe exudative AMD.
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