Lebriz Altay1, Paula Scholz2, Tina Schick2, Moritz Felsch3, Carel B Hoyng4, Anneke I den Hollander5, Thomas Langmann6, Sascha Fauser2. 1. Department of Ophthalmology University Hospital of Cologne, Cologne, Germany 2Experimental Immunology of the Eye, Department of Ophthalmology, University of Cologne, Cologne, Germany. 2. Department of Ophthalmology University Hospital of Cologne, Cologne, Germany. 3. Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Cologne, Germany. 4. Department of Ophthalmology, Radboud University Medical Center, Nijmegen, The Netherlands. 5. Department of Ophthalmology, Radboud University Medical Center, Nijmegen, The Netherlands 5Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands. 6. Experimental Immunology of the Eye, Department of Ophthalmology, University of Cologne, Cologne, Germany.
Abstract
PURPOSE: We evaluated the association of hyperreflective foci (HF) observed in early and intermediate age-related macular degeneration (AMD) with known AMD risk alleles. METHODS: In this pilot case-control study, HF were defined as lesions with reflectivity equal or higher than the retinal pigment epithelium band in spectral domain optical coherence tomography (SDOCT). Hyperreflective foci in the outer nuclear layer and photoreceptor complex were evaluated in 518 individuals with early and intermediate AMD. Definite presence of HF was defined as at least 10 HF in all SDOCT scans. Genotyping was performed for 22 single nucleotide polymorphisms (SNPs). Associations between AMD severity stages, HF, and SNPs were determined by logistic regression analyses. RESULTS: Hyperreflective foci (n ≥ 10) were significantly associated with AMD severity and the association was strongest with intermediate AMD (odds ratio [OR], 8.45; P = 1.092*10-8). Independently, HF showed associations with ARMS2 rs104909/HtRA1 rs11200638 (OR, 1.64; P = 0.017), CFH rs1061170 (OR, 1.70; P = 0.011), and APOE4/TOMM40 rs2075650 (OR, 2.26; P = 0.005) variants. Within the group of intermediate AMD, associations were similar (ARMS2 rs104909/HtRA1 rs11200638 OR, 1.79, P = 0.010; CFH rs1061170 OR, 1.77, P = 0.013; APOE4/TOMM40 rs2075650 OR, 1.98; P = 0.034) and showed additional trending associations with VEGFA rs943080 variant (OR, 0.59; P = 0.024). After Bonferroni-correction for 22 SNPs, none of the associations was statistically significant (P ≤ 0.0023). CONCLUSIONS: The presence of HF is related to AMD severity. Despite limited power of this pilot study, our results suggest an association of HF with polymorphisms in ARMS2/HTRA1, CFH, APOE4/TOMM40, and VEGFA genes which could be triggered by modification of the extracellular matrix, altered complement system or lipid metabolism.
PURPOSE: We evaluated the association of hyperreflective foci (HF) observed in early and intermediate age-related macular degeneration (AMD) with known AMD risk alleles. METHODS: In this pilot case-control study, HF were defined as lesions with reflectivity equal or higher than the retinal pigment epithelium band in spectral domain optical coherence tomography (SDOCT). Hyperreflective foci in the outer nuclear layer and photoreceptor complex were evaluated in 518 individuals with early and intermediate AMD. Definite presence of HF was defined as at least 10 HF in all SDOCT scans. Genotyping was performed for 22 single nucleotide polymorphisms (SNPs). Associations between AMD severity stages, HF, and SNPs were determined by logistic regression analyses. RESULTS: Hyperreflective foci (n ≥ 10) were significantly associated with AMD severity and the association was strongest with intermediate AMD (odds ratio [OR], 8.45; P = 1.092*10-8). Independently, HF showed associations with ARMS2 rs104909/HtRA1rs11200638 (OR, 1.64; P = 0.017), CFHrs1061170 (OR, 1.70; P = 0.011), and APOE4/TOMM40rs2075650 (OR, 2.26; P = 0.005) variants. Within the group of intermediate AMD, associations were similar (ARMS2 rs104909/HtRA1rs11200638 OR, 1.79, P = 0.010; CFHrs1061170 OR, 1.77, P = 0.013; APOE4/TOMM40rs2075650 OR, 1.98; P = 0.034) and showed additional trending associations with VEGFArs943080 variant (OR, 0.59; P = 0.024). After Bonferroni-correction for 22 SNPs, none of the associations was statistically significant (P ≤ 0.0023). CONCLUSIONS: The presence of HF is related to AMD severity. Despite limited power of this pilot study, our results suggest an association of HF with polymorphisms in ARMS2/HTRA1, CFH, APOE4/TOMM40, and VEGFA genes which could be triggered by modification of the extracellular matrix, altered complement system or lipid metabolism.
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