Typical exudative AMD and RAP: From genotype to phenotype

Session Details

Session Title: Free Paper Session 9: AMD III

Session Date/Time: Friday 08/09/2017 | 08:00-09:30

Paper Time: 08:24

Venue: Room 117

First Author: : J.Marques PORTUGAL

Co Author(s): :    M. Tomas   M. Raimundo   M. Marques   L. Pires   I. Carreira   R. Silva              

Abstract Details


To identify genetic biomarkers of typical exudative age-related macular degeneration (eAMD) and retinal angiomatous proliferation (RAP) using multiplex ligation-dependent probe amplification (MLPA).


Department of Ophthalmology, Centro Hospitalar e Universitário de Coimbra (CHUC); Association for Innovation and Biomedical Research on Light and Image (AIBILI); Faculty of Medicine, University of Coimbra (FMUC); Cytogenetics and Genomics Laboratory, Faculty of Medicine University of Coimbra


Cross-sectional study. One hundred and seventy two subjects, comprising RAP, eAMD and controls were included. Multimodal retinal imaging was used to differentiate between RAP and eAMD cases. The control group included subjects without AMD (n=83) and patients with early/intermediate AMD (n=16). The study adhered to the tenets of the declaration of Helsinki. Peripheral blood was collected and the samples were sent to the Citogenetics and Genomics Laboratory of the Faculty of Medicine, University of Coimbra. DNA extraction was performed using commercial kits: Jetquick blood and cell culture DNA Midi Spin Kit and GeneCatcherTM gDNA 3-10 mL Blood Kit. The presence of SNPs and CNVs was evaluated using a SALSA MLPA probemix (P236 ARMD mix-1), covering the most frequent susceptibility loci for AMD. The homozygous presence/absence of the risk alleles was evaluated. Logistic regressions were used to estimate the effect of each genetic variant in the development of RAP and eAMD. P-values ≤0.05 were considered statistically significant.


Subjects were divided in 3 groups: group A – RAP (n=39; 83.2±6.5 years old), group B – eAMD (n=34; 81.1±7.6 years old) and group C – control (n=99; 71.8±6.6 years old). A statistically significant difference between cases (eAMD+RAP) and controls was found for the CFH intronic SNP (rs1410996), ARMS2 SNP A69S (rs10490924) and CNVs in the CFHR3-1 genes. The combination of ≥3 genetic variants was found to be significantly associated with the neovascular phenotypes (p<0.001, OR=3.44, 95% CI [1.82 – 6.50]). The CFH intronic SNP (rs1410996) was the only genetic variant able to significantly differentiate eAMD from RAP (p=0.046, OR=2.64, 95% CI [1.01–6.81]). However, an integrated analysis of genetic risk variants showed that the homozygous presence of both the CFH SNP Y402H (rs1061170) and the CFH intronic SNP (rs1410996) confers an increased risk of eAMD over RAP (p=0.031, OR=2.86, 95% CI [1.10 – 7.42]). An identical result was found for the homozygous presence of both the CFH SNP Y402H (rs1061170) and the CFH intronic SNP (rs1410996) along with the absence of CNVs in the CFHR3-1 genes (p=0.031, OR=2.86, 95% CI [1.10 – 7.42]).


AMD is a multifactorial disease characterized by complex genetic and environmental interactions. This study has demonstrated that patients with neovascular phenotypes of AMD can be easily distinguished from controls on a genetic basis. The CFH intronic SNP (rs1410996) appears to play an important role in the distinction between eAMD and RAP. However, the combination of several genetic risk variants emerges as a better biomarker of eAMD. The combined presence of the CFH SNP Y402H (rs1061170) and the CFH intronic SNP (rs1410996) along with the absence of CNVs in the CFHR3-1 genes were shown to be significantly associated with eAMD over RAP.

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