Phenotypic Expression of CFH Rare Variants in Age-Related Macular Degeneration Patients in the Coimbra Eye Study.

Autor:	Farinha C; AIBILI-Association for Innovation and Biomedical Research on Light and Image, Coimbra, Portugal.; Ophthalmology Department, Centro Hospitalar e Universitário de Coimbra (CHUC), Coimbra, Portugal.; Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal.; University of Coimbra, Coimbra Institute for Clinical and Biomedical Research. Faculty of Medicine (iCBR- FMUC), Coimbra, Portugal., Barreto P; AIBILI-Association for Innovation and Biomedical Research on Light and Image, Coimbra, Portugal., Coimbra R; AIBILI-Association for Innovation and Biomedical Research on Light and Image, Coimbra, Portugal., Iutis A; Department of Mathematics, University of Aveiro, Aveiro, Portugal., Cachulo ML; AIBILI-Association for Innovation and Biomedical Research on Light and Image, Coimbra, Portugal.; Ophthalmology Department, Centro Hospitalar e Universitário de Coimbra (CHUC), Coimbra, Portugal.; Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal.; University of Coimbra, Coimbra Institute for Clinical and Biomedical Research. Faculty of Medicine (iCBR- FMUC), Coimbra, Portugal., Cunha-Vaz J; AIBILI-Association for Innovation and Biomedical Research on Light and Image, Coimbra, Portugal.; Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal.; University of Coimbra, Coimbra Institute for Clinical and Biomedical Research. Faculty of Medicine (iCBR- FMUC), Coimbra, Portugal., Lechanteur YTE; Department of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands., Hoyng CB; Department of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands., Silva R; AIBILI-Association for Innovation and Biomedical Research on Light and Image, Coimbra, Portugal.; Ophthalmology Department, Centro Hospitalar e Universitário de Coimbra (CHUC), Coimbra, Portugal.; Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal.; University of Coimbra, Coimbra Institute for Clinical and Biomedical Research. Faculty of Medicine (iCBR- FMUC), Coimbra, Portugal.
Jazyk:	angličtina
Zdroj:	Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 2022 Aug 02; Vol. 63 (9), pp. 5.
DOI:	10.1167/iovs.63.9.5
Abstrakt:	Purpose: To determine the association between rare genetic variants in complement factor H (CFH) and phenotypic features in age-related macular degeneration (AMD) patients from the Coimbra Eye Study (CES). Methods: AMD patients from the Incidence CES (NCT02748824) underwent ophthalmologic examination and color fundus photography, spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence, and near-infrared imaging. Multimodal phenotypic characterization was carried out in a centralized reading center. The coding and splice-site regions of the CFH gene were sequenced through single-molecule molecular inversion probe-based next-generation sequencing in association with the EYE-RISK consortium. Variants with minor allele frequency <0.05 resulting in splice-site or protein change were selected. Differences in phenotypic features between carriers and noncarriers were analyzed using generalized estimated equations logistic regression models, considering intereye correlations. Results: We included 39 eyes of 23 patients carrying rare CFH variants and 284 eyes of 188 noncarriers. Carrier status was associated with having higher drusen burden in the macula in the inner Early Treatment Diabetic Retinopathy Study circle (odds ratio [OR], 5.44 [95% confidence interval {CI}, 1.61-18.37]; P = 0.006), outer circle (OR, 4.37 [95% CI, 1.07-17.77]; P = 0.04), and full grid (OR, 4.82 [95% CI, 1.13-20.52]; P = 0.033). In SD-OCT, a lower total macular volume and lower inner retinal layers' volume (OR, 0.449 [95% CI, 0.226-0.894]; P = 0.023; OR, 0.496 [95% CI, 0.252-0.979]; P = 0.043) and pigment epithelial detachments (PEDs) (OR, 5.24 [95% CI, 1.08-25.44]; P = 0.04) were associated with carrying a rare CFH variant. Carriers with subretinal drusenoid deposits (SDD) had the rare variant P258L in all cases except one. Conclusions: We identified in our cohort phenotypic differences between carriers and noncarriers of rare variants in the CFH gene. Carriers had more severe disease, namely superior drusen burden, PEDs, and thinner retinas. The rare variant P258L may be associated with SDD. Carriers are probably at increased risk of progression.
Databáze:	MEDLINE
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