Fleckenstein, Monika and Grassmann, Felix and Lindner, Moritz and Pfau, Maximilian and Czauderna, Joanna and Strunz, Tobias and von Strachwitz, Claudia and Schmitz-Valckenberg, Steffen and Holz, Frank G. and Weber, Bernhard H. F. (2016) Distinct Genetic Risk Profile of the Rapidly Progressing Diffuse-Trickling Subtype of Geographic Atrophy in Age-Related Macular Degeneration (AMD). INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 57 (6). pp. 2463-2471. ISSN 0146-0404, 1552-5783
Full text not available from this repository. (Request a copy)Abstract
PURPOSE. To genetically characterize a subphenotype of geographic atrophy (GA) in AMD associated with rapid progression and a diffuse-trickling appearance on fundus autofluorescence imaging. METHODS. Patients from the Fundus Autofluorescence in Age-Related Macular Degeneration Study were phenotyped for diffuse-trickling GA (dt-GA; n = 44). DNA was analyzed for 10 known AMD-associated genetic variants. A genetic risk score (GRS) was calculated and compared with patients with nondiffuse-trickling GA (ndt-GA; n = 311) and individuals from the 1000 genomes project (1000G; n = 267). Given the phenotypic overlap between diffuse trickling and late-onset retinal degeneration (LORD), all C1QTNF5 exons and their exon/ intron boundaries were sequenced. RESULTS. A statistically significant difference in allele frequencies between dt-GA and ndt-GA were found for CFH: rs1061170 and CFH: rs800292 (P-corrected = 0.03). The ARMS2 variant rs10490924 was significantly more frequent in dt-GA than in 1000G individuals (P-corrected < 0.01). The GRS of dt-GA patients was in-between the score of the 1000G individuals and that of patients with ndt-GA, significantly differing from both (P-corrected < 0.01). Sequencing of C1QTNF5 revealed 28 unique variants although none showed a statistically significant association with dt-GA when compared with 1000G individuals. CONCLUSIONS. The dt-GA phenotype shows a remarkably different genetic risk profile from other GA phenotypes secondary to AMD. Disease-associated C1QTNF5 mutations were not identified. Together, these results suggest that the dt-GA phenotype is associated with a genetic background substantially different from other GA phenotypes and underlines the necessity to refine the clinical phenotyping, specifically when aiming for individualized therapies in AMD.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ONSET RETINAL DEGENERATION; PIGMENT-EPITHELIUM DEPOSITS; GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY VARIANTS; MUTATION; C1QTNF5; DISEASE; DRUSEN; MODEL; CTRP5; AMD; fundus autofluorescence imaging; diffuse-trickling phenotype; late-onset retinal degeneration; C1QTNF5 gene; genetic risk factors |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Humangenetik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Mar 2019 06:40 |
| Last Modified: | 22 Mar 2019 06:40 |
| URI: | https://pred.uni-regensburg.de/id/eprint/2968 |
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