CIDEC: A Potential Factor in Diabetic Vascular Inflammation

Song, Fang-qiang; Zhou, Huimin; Ma, Weixuan; Li, Yulin; Hu, Bo-ang; Shang, Yuan-yuan; Wang, Zhi-Hao; Zhong, Ming; Zhang, Wei; Ti, Yun

doi:10.1159/000520685

Cited by 2 publications

(2 citation statements)

References 22 publications

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“…This points out toward a “systemic” effect of the beneficial Q1 AMD CIDEC variants. Interestingly, a similar indirect and systemic favorable effect has recently been reported in mouse models of vascular inflammation and atherogenesis after Fsp27 silencing 38; 39 . Many studies on dietary or circulating lipids, as well as genetic studies support a role for not only local lipid trafficking in the retina but also for circulating lipoproteins in AMD pathogenesis 40 .…”

Section: Discussionsupporting

confidence: 75%

Age-related Macular Degeneration patient deep phenotyping and whole genome sequencing analysis identifies coding variants linking small low-luminance visual deficit to fat storage defects

Kim

Stockwell²,

Qin³

et al. 2022

Preprint

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Background: 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 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.

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Section: Discussionsupporting

confidence: 75%

Age-related Macular Degeneration patient deep phenotyping and whole genome sequencing analysis identifies coding variants linking small low-luminance visual deficit to fat storage defects

Kim

Stockwell²,

Qin³

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…This points out toward a “systemic” effect of the beneficial Q1 AMD CIDEC variants. Interestingly, a similar indirect and systemic favorable effect has recently been reported in mouse models of vascular inflammation and atherogenesis after Fsp27 silencing [ 39 , 40 ]. Many studies on dietary or circulating lipids, as well as genetic studies support a role for not only local lipid trafficking in the retina but also for circulating lipoproteins in AMD pathogenesis [ 41 ].…”

Section: Discussionsupporting

confidence: 63%

Rare CIDEC coding variants enriched in age-related macular degeneration patients with small low-luminance deficit cause lipid droplet and fat storage defects

Kim¹,

Stockwell²,

Qin³

et al. 2023

PLoS ONE

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Background 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.

show abstract

CIDEC: A Potential Factor in Diabetic Vascular Inflammation

Cited by 2 publications

References 22 publications

Age-related Macular Degeneration patient deep phenotyping and whole genome sequencing analysis identifies coding variants linking small low-luminance visual deficit to fat storage defects

Age-related Macular Degeneration patient deep phenotyping and whole genome sequencing analysis identifies coding variants linking small low-luminance visual deficit to fat storage defects

Rare CIDEC coding variants enriched in age-related macular degeneration patients with small low-luminance deficit cause lipid droplet and fat storage defects

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