Associations of genetically determined lipid traits and lipid-modifying agents with the risk of diabetic retinopathy : A Mendelian randomization study
Li, Ning ; Zhang, Xiaoyu ; Zhang, Meng ; Wu, Lijuan ; Li, Changwei ; Pan, Yuesong ; Wang, Wei ; Ji, Jianguang LU
and Zheng, Deqiang
LU
(2023)
In Atherosclerosis
369.
p.9-16
- Abstract
BACKGROUND AND AIMS: The evidence that dyslipidemia is associated with hyperglycemia calls for an investigation of whether dyslipidemia, as well as lipid-modifying agents, could affect the subsequent development of diabetic retinopathy (DR). Therefore, we aimed to address these unanswered questions by utilizing Mendelian randomization (MR) analysis.
METHODS: Genetic variants were selected from the UK Biobank as instruments to serve as proxies for lipid traits [high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), apolipoprotein A-I (APOA-I) and apolipoprotein B (APOB)]. Univariable and multivariable MR analyses were performed to examine the associations of these lipid traits... (More)
BACKGROUND AND AIMS: The evidence that dyslipidemia is associated with hyperglycemia calls for an investigation of whether dyslipidemia, as well as lipid-modifying agents, could affect the subsequent development of diabetic retinopathy (DR). Therefore, we aimed to address these unanswered questions by utilizing Mendelian randomization (MR) analysis.
METHODS: Genetic variants were selected from the UK Biobank as instruments to serve as proxies for lipid traits [high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), apolipoprotein A-I (APOA-I) and apolipoprotein B (APOB)]. Univariable and multivariable MR analyses were performed to examine the associations of these lipid traits with DR and different levels of severity of DR. Based on the evidence for the effects of lipids on outcomes, we estimated the causal relevance of cholesteryl ester transfer protein (CETP) inhibitors in severe nonproliferative and proliferative DR using protein quantitative trait loci (pQTLs) and expression quantitative trait loci (eQTLs) as instruments.
RESULTS: Genetically determined HDL-C levels were inversely associated with the risk of severe nonproliferative DR (OR = 0.70, 95% CI = 0.52-0.94) and proliferative DR (OR = 0.90, 95% CI = 0.83-0.97) in the main analyses utilizing the inverse variance-weighted (IVW) MR method and a couple of sensitivity analyses. No association was noted between genetically proxied CETP inhibitors and DR.
CONCLUSIONS: This MR study suggests the casual protective roles of HDL-C in severe nonproliferative DR and proliferative DR, which calls for further studies to confirm these findings. Current lipid-modifying agents acting on HDL-C may not reduce the risk of DR and new treatments are required in the future.
(Less)
- author
- Li, Ning
; Zhang, Xiaoyu
; Zhang, Meng
; Wu, Lijuan
; Li, Changwei
; Pan, Yuesong
; Wang, Wei
; Ji, Jianguang
LU
and Zheng, Deqiang
LU
- organization
- publishing date
- 2023-02-11
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Atherosclerosis
- volume
- 369
- pages
- 9 - 16
- publisher
- Elsevier
- external identifiers
-
- scopus:85148759648
- pmid:36827905
- ISSN
- 1879-1484
- DOI
- 10.1016/j.atherosclerosis.2023.02.001
- language
- English
- LU publication?
- yes
- additional info
- Copyright © 2023 Elsevier B.V. All rights reserved.
- id
- 2ec889e6-c716-4a34-a83a-271dd41a7da0
- date added to LUP
- 2023-03-02 16:12:10
- date last changed
- 2024-06-13 10:56:01
@article{2ec889e6-c716-4a34-a83a-271dd41a7da0,
abstract = {{<p>BACKGROUND AND AIMS: The evidence that dyslipidemia is associated with hyperglycemia calls for an investigation of whether dyslipidemia, as well as lipid-modifying agents, could affect the subsequent development of diabetic retinopathy (DR). Therefore, we aimed to address these unanswered questions by utilizing Mendelian randomization (MR) analysis.</p><p>METHODS: Genetic variants were selected from the UK Biobank as instruments to serve as proxies for lipid traits [high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), apolipoprotein A-I (APOA-I) and apolipoprotein B (APOB)]. Univariable and multivariable MR analyses were performed to examine the associations of these lipid traits with DR and different levels of severity of DR. Based on the evidence for the effects of lipids on outcomes, we estimated the causal relevance of cholesteryl ester transfer protein (CETP) inhibitors in severe nonproliferative and proliferative DR using protein quantitative trait loci (pQTLs) and expression quantitative trait loci (eQTLs) as instruments.</p><p>RESULTS: Genetically determined HDL-C levels were inversely associated with the risk of severe nonproliferative DR (OR = 0.70, 95% CI = 0.52-0.94) and proliferative DR (OR = 0.90, 95% CI = 0.83-0.97) in the main analyses utilizing the inverse variance-weighted (IVW) MR method and a couple of sensitivity analyses. No association was noted between genetically proxied CETP inhibitors and DR.</p><p>CONCLUSIONS: This MR study suggests the casual protective roles of HDL-C in severe nonproliferative DR and proliferative DR, which calls for further studies to confirm these findings. Current lipid-modifying agents acting on HDL-C may not reduce the risk of DR and new treatments are required in the future.</p>}},
author = {{Li, Ning and Zhang, Xiaoyu and Zhang, Meng and Wu, Lijuan and Li, Changwei and Pan, Yuesong and Wang, Wei and Ji, Jianguang and Zheng, Deqiang}},
issn = {{1879-1484}},
language = {{eng}},
month = {{02}},
pages = {{9--16}},
publisher = {{Elsevier}},
series = {{Atherosclerosis}},
title = {{Associations of genetically determined lipid traits and lipid-modifying agents with the risk of diabetic retinopathy : A Mendelian randomization study}},
url = {{http://dx.doi.org/10.1016/j.atherosclerosis.2023.02.001}},
doi = {{10.1016/j.atherosclerosis.2023.02.001}},
volume = {{369}},
year = {{2023}},
}