PMID- 35925583
OWN - NLM
STAT- MEDLINE
DCOM- 20220808
LR  - 20220825
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 63
IP  - 9
DP  - 2022 Aug 2
TI  - Phenotypic Expression of CFH Rare Variants in Age-Related Macular Degeneration 
      Patients in the Coimbra Eye Study.
PG  - 5
LID - 10.1167/iovs.63.9.5 [doi]
LID - 5
AB  - 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.
FAU - Farinha, Claudia
AU  - Farinha C
AD  - AIBILI-Association for Innovation and Biomedical Research on Light and Image, 
      Coimbra, Portugal.
AD  - Ophthalmology Department, Centro Hospitalar e Universitario de Coimbra (CHUC), 
      Coimbra, Portugal.
AD  - Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal.
AD  - University of Coimbra, Coimbra Institute for Clinical and Biomedical Research. 
      Faculty of Medicine (iCBR- FMUC), Coimbra, Portugal.
FAU - Barreto, Patricia
AU  - Barreto P
AD  - AIBILI-Association for Innovation and Biomedical Research on Light and Image, 
      Coimbra, Portugal.
FAU - Coimbra, Rita
AU  - Coimbra R
AD  - AIBILI-Association for Innovation and Biomedical Research on Light and Image, 
      Coimbra, Portugal.
FAU - Iutis, Adela
AU  - Iutis A
AD  - Department of Mathematics, University of Aveiro, Aveiro, Portugal.
FAU - Cachulo, Maria Luz
AU  - Cachulo ML
AD  - AIBILI-Association for Innovation and Biomedical Research on Light and Image, 
      Coimbra, Portugal.
AD  - Ophthalmology Department, Centro Hospitalar e Universitario de Coimbra (CHUC), 
      Coimbra, Portugal.
AD  - Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal.
AD  - University of Coimbra, Coimbra Institute for Clinical and Biomedical Research. 
      Faculty of Medicine (iCBR- FMUC), Coimbra, Portugal.
FAU - Cunha-Vaz, Jose
AU  - Cunha-Vaz J
AD  - AIBILI-Association for Innovation and Biomedical Research on Light and Image, 
      Coimbra, Portugal.
AD  - Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal.
AD  - University of Coimbra, Coimbra Institute for Clinical and Biomedical Research. 
      Faculty of Medicine (iCBR- FMUC), Coimbra, Portugal.
FAU - Lechanteur, Yara T E
AU  - Lechanteur YTE
AD  - Department of Ophthalmology, Donders Institute for Brain, Cognition and 
      Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
FAU - Hoyng, Carel B
AU  - Hoyng CB
AD  - Department of Ophthalmology, Donders Institute for Brain, Cognition and 
      Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
FAU - Silva, Rufino
AU  - Silva R
AD  - AIBILI-Association for Innovation and Biomedical Research on Light and Image, 
      Coimbra, Portugal.
AD  - Ophthalmology Department, Centro Hospitalar e Universitario de Coimbra (CHUC), 
      Coimbra, Portugal.
AD  - Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal.
AD  - University of Coimbra, Coimbra Institute for Clinical and Biomedical Research. 
      Faculty of Medicine (iCBR- FMUC), Coimbra, Portugal.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 80295-65-4 (Complement Factor H)
SB  - IM
MH  - Complement Factor H/genetics
MH  - Fluorescein Angiography/methods
MH  - Humans
MH  - *Macula Lutea
MH  - *Macular Degeneration/diagnosis/epidemiology/genetics
MH  - *Retinal Detachment
MH  - *Retinal Drusen/diagnosis
MH  - Tomography, Optical Coherence/methods
PMC - PMC9363674
COIS- Disclosure: C. Farinha, Novartis (C), Bayer (C); P. Barreto, None; R. Coimbra, 
      None; A. Iutis, None; M.L. Cachulo, Bayer (C), Novartis (C); J. Cunha-Vaz, 
      Precision Ocular Ltd (C), Roche (C), Carl Zeiss Meditec (C), AlimeraSciences (C), 
      Allergan (C), Bayer (C), Gene Signal (C), Novartis (C), Pfizer (C), 
      Sanofi-Aventis (C), Vifor Pharma (C); Y.T.E. Lechanteur, Novartis (C), Bayer (C); 
      C.B. Hoyng, Bayer (C), Novartis (C), Horus Pharma Abbvie (C), Horama (C), 
      Astherna (F); R. Silva, Bayer (C), Alcon (C), Thea (C), Novartis (C), Alimera 
      Sciences (C), Allergan (C)
EDAT- 2022/08/05 06:00
MHDA- 2022/08/09 06:00
PMCR- 2022/08/04
CRDT- 2022/08/04 11:33
PHST- 2022/08/04 11:33 [entrez]
PHST- 2022/08/05 06:00 [pubmed]
PHST- 2022/08/09 06:00 [medline]
PHST- 2022/08/04 00:00 [pmc-release]
AID - 2783543 [pii]
AID - IOVS-22-35009 [pii]
AID - 10.1167/iovs.63.9.5 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2022 Aug 2;63(9):5. doi: 10.1167/iovs.63.9.5.