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. 2024 May 9:2024:5324127.
doi: 10.1155/2024/5324127. eCollection 2024.

Genetic Association between Lipid-Regulating Drug Targets and Diabetic Retinopathy: A Drug Target Mendelian Randomization Study

Shengnan Chen  1   2 , Ming Zhang  3 , Peng Yang  1 , Jianbin Guo  1 , Lin Liu  1 , Zhi Yang  1 , Kai Nan  1
Affiliations

Genetic Association between Lipid-Regulating Drug Targets and Diabetic Retinopathy: A Drug Target Mendelian Randomization Study

Shengnan Chen et al. J Lipids. .

Abstract

Background: Diabetic retinopathy (DR) is a diabetic microvascular complication and a leading cause of vision loss. However, there is a lack of effective strategies to reduce the risk of DR currently. The present study is aimed at assessing the causal effect of lipid-regulating targets on DR risk using a two-sample Mendelian randomization (MR) study.

Method: Genetic variants within or near drug target genes, including eight lipid-regulating targets for LDL-C (HMGCR, PCSK9, and NPC1L1), HDL-C (CETP, SCARB1, and PPARG), and TG (PPARA and LPL), were selected as exposures. The exposure data were obtained from the IEU OpenGWAS project. The outcome dataset related to DR was obtained from the FinnGen research project. Inverse-variance-weighted MR (IVW-MR) was used to calculate the effect estimates by each target. Sensitivity analyses were performed to verify the robustness of the results.

Results: There was suggestive evidence that PCSK9-mediated LDL-C levels were positively associated with DR, with OR (95% CI) of 1.34 (1.02-1.77). No significant association was found between the expression of HMGCR- and NPC1L1-mediated LDL-C levels; CETP-, SCARB1-, and PPARG-mediated HDL-C levels; PPARA- and LPL-mediated TG levels; and DR risk.

Conclusions: This is the first study to reveal a genetically causal relationship between lipid-regulating drug targets and DR risk. PCSK9-mediated LDL-C levels maybe positively associated with DR risk at the genetic level. This study provides suggestive evidence that PCSK9 inhibition may reduce the risk of DR.

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Conflict of interest statement

The authors declare that there is no conflict of interest regarding the publication of this paper.

Figures

Figure 1
Figure 1
Association between lipid-regulating drug targets and DR risk.
Figure 2
Figure 2
Scatter plot for drug targets: (a) HMGCR-, (b) PCSK9-, and (c) NPC1L1-mediated LDL-C effects on DR.
Figure 3
Figure 3
Scatter plot for drug targets: (a) CETP-, (b) SCARB1-, and (c) PPARG-mediated HDL-C effects on DR.
Figure 4
Figure 4
Scatter plot for drug targets: (a) PPARA- and (b) LPL-mediated TG effects on DR.
See this image and copyright information in PMC

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