Genetic characterization of a Portuguese age-related macular degeneration population

Abstract

Purpose : The purpose of this study was to genetically characterize an AMD population from Portugal.

Methods : We performed the epidemiological Coimbra Eye Study (NCT02748824), and genotyped AMD patients and controls. Participants were classified based on the Rotterdam Classification. Patients were considered stages 2,3 and 4, whereas controls were considered stages 0 and 1b. For this analysis, we considered 243 patients and 598 controls. Genotyping was performed using a single-molecule molecular inversion probes and next generation sequencing to target single nucleotide polymorphisms (SNPs) and coding and splice-site regions of 13 genes: ARMS2, C3, C9, CD46, CFB, CFH, CFI, HTRA1, TIMP3, SLC16A8, ABCA4, CTNNA1, and PRPH2. The genetic assay was performed under the EyeRisk Project, of the E3 Consortium. A total of 841 samples and 69 SNPs were tested for association under an additive model, using the presence of AMD as a binary outcome. A logistic regression analysis was performed to assess allelic odds ratio (ORs) at 95% CI for each variant, adjusted for age and sex.

Results : We have identified 7 variants that may have a protective effect on the outcome of the disease: C2_CFB_SKIV2L rs429608 (OR 0.518;CI 95% 0.342-0.765, p= 0.0013); CFH rs10922109 (OR 0.683;CI 95% 0.5657-0.891, p= 0.0032) and rs1410996 (OR 0.708;CI 95% 0.5629-0.886, p=0.0028); CETP rs5817082 (OR 0.738;CI 95% 0.5637-0.961, p= 0.0255); CNN2 rs10422209 (OR 0.683;CI 95% 0.4757-0.966, p= 0.0343; CB rs641153 (OR 0.659;CI 95% 0.4408-0.966, p= 0.0366) and RDBP_CFB rs760070 (OR 0.682;CI 95% 0.4565-0.997, p=0.0541).
Additionally, we have identified 4 SNPs associated with the presence of AMD: ARMS2 rs10490924 (OR 1.51; CI 95% 1,1369 - 2, p= 0,0042); ARMS2_HTRA1 rs3750846 (OR 1.5; CI 95% 1.1226- 1.99, p= 0.0057); SLC16A8 rs8135665 (OR 1.51; CI 95% 1.0893- 2.08, p= 0.0128) and CFH rs35292876 (OR 2.93; CI 95% 1.204- 7.15, p= 0.0166).

Conclusions : Our results are in line with other studies that have been published, namely the two major genetic studies of the IAMDGC and the EyeRisk Project, highlighting the importance of genetics in the disease. The genes associated with AMD act in different pathophysiology pathways, sustaining the multifactorial etiology of AMD. To our knowledge, this is the first genetic study of a Portuguese AMD population, and our results are compliant with literature.

This is a 2021 ARVO Annual Meeting abstract.