In:
PLOS ONE, Public Library of Science (PLoS), Vol. 18, No. 4 ( 2023-4-20), p. e0280484-
Abstract:
The basis of Age-related macular degeneration (AMD) genetic risk has been well documented; however, few studies have looked at genetic biomarkers of disease progression or treatment response within advanced AMD patients. Here we report the first genome-wide analysis of genetic determinants of low-luminance vision deficit (LLD), which is seen as predictive of visual acuity loss and anti-VEGF treatment response in neovascular AMD patients. Methods AMD patients were separated into small- and large-LLD groups for comparison and whole genome sequencing was performed. Genetic determinants of LLD were assessed by common and rare variant genetic analysis. Follow-up functional analysis of rare coding variants identified by the burden test was then performed in vitro . Results We identified four coding variants in the CIDEC gene. These rare variants were only present in patients with a small LLD, which has been previously shown to indicate better prognosis and better anti-VEGF treatment response. Our in vitro functional characterization of these CIDEC alleles revealed that all decrease the binding affinity between CIDEC and the lipid droplet fusion effectors PLIN1, RAB8A and AS160. The rare CIDEC alleles all cause a hypomorphic defect in lipid droplet fusion and enlargement, resulting in a decreased fat storage capability in adipocytes. Conclusions As we did not detect CIDEC expression in the ocular tissue affected by AMD, our results suggest that the CIDEC variants do not play a direct role in the eye and influence low-luminance vision deficit via an indirect and systemic effect related to fat storage capacity.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0280484
DOI:
10.1371/journal.pone.0280484.g001
DOI:
10.1371/journal.pone.0280484.g002
DOI:
10.1371/journal.pone.0280484.g003
DOI:
10.1371/journal.pone.0280484.g004
DOI:
10.1371/journal.pone.0280484.g005
DOI:
10.1371/journal.pone.0280484.g006
DOI:
10.1371/journal.pone.0280484.g007
DOI:
10.1371/journal.pone.0280484.g008
DOI:
10.1371/journal.pone.0280484.t001
DOI:
10.1371/journal.pone.0280484.t002
DOI:
10.1371/journal.pone.0280484.t003
DOI:
10.1371/journal.pone.0280484.s001
DOI:
10.1371/journal.pone.0280484.s002
DOI:
10.1371/journal.pone.0280484.s003
DOI:
10.1371/journal.pone.0280484.s004
DOI:
10.1371/journal.pone.0280484.s005
DOI:
10.1371/journal.pone.0280484.s006
DOI:
10.1371/journal.pone.0280484.r001
DOI:
10.1371/journal.pone.0280484.r002
DOI:
10.1371/journal.pone.0280484.r003
DOI:
10.1371/journal.pone.0280484.r004
DOI:
10.1371/journal.pone.0280484.r005
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2267670-3
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