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Observational Study
. 2024 Mar 22;22(1):298.
doi: 10.1186/s12967-024-05097-8.

Statins as a risk factor for diabetic retinopathy: a Mendelian randomization and cross-sectional observational study

Chengming Chen #  1   2 , Huan Zhang #  3 , Yanyan Lan #  4 , Weiming Yan #  4 , Sida Liu  1 , Yixuan Chen  1 , Tingke Xie  1 , Jiayi Ning  1 , Xiaolong Yan  5 , Lei Shang  6 , Jing Han  7
Affiliations
Observational Study

Statins as a risk factor for diabetic retinopathy: a Mendelian randomization and cross-sectional observational study

Chengming Chen et al. J Transl Med. .

Abstract

Background: Diabetic retinopathy (DR) is the foremost cause of vision loss among the global working-age population, and statins are among the most frequently prescribed drugs for lipid management in patients with DR. The exact relationship between statins and DR has not been determined. This study sought to validate the causal association between statins usage and diabetic retinopathy.

Methods: The summary-data-based Mendelian randomization (SMR) method and inverse-variance-weighted Mendelian randomization (IVW-MR) were used to identify the causal relationship between statins and DR via the use of expression quantitative trait loci (eQTL) data for 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) (31,684 blood samples), low density lipoprotein cholesterol-related GWAS data (sample size: 440,546), and DR-related GWAS data (14,584 cases and 176,010 controls). Additionally, a cross-sectional observational study based on the data from the National Health and Nutrition Examination Survey (NHANES) was conducted to supplement the association between DR and statins (sample size: 106,911). The odds ratios (ORs) with corresponding 95% confidence intervals (CIs) was employed to evaluate the results.

Results: Based on the results of the MR analysis, HMGCR inhibitors were causally connected with a noticeably greater incidence of DR (IVW: OR = 0.54, 95% CI [0.42, 0.69], p = 0.000002; SMR: OR = 0.66, 95% CI [0.52, 0.84], p = 0.00073). Subgroup analysis revealed that the results were not affected by the severity of DR. The sensitivity analysis revealed the stability and reliability of the MR analysis results. The results from the cross-sectional study based on NHANES also support the association between not taking statins and a decreased risk of DR (OR = 0.54, 95% CI [0.37, 0.79], p = 0.001).

Conclusions: This study revealed that a significant increase in DR risk was causally related to statins use, providing novel insights into the role of statins in DR. However, further investigations are needed to verify these findings.

Keywords: Diabetic retinopathy; HMGCR; Mendelian randomization; NHANES; Statins.

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Conflict of interest statement

Chengming Chen, Huan Zhang, Yanyan Lan, Weiming Yan, Sida, Liu, Yixuan Chen, Tingke Xie, Jiayi Ning, Xiaolong Yan, Lei Shang and Jing Han declare no interest conflicts among them.

Figures

Fig. 1
Fig. 1
Schematic diagram of IVW-MR and SMR. DR: Diabetic retinopathy; NPDR: Non-proliferative diabetic retinopathy; PDR: Proliferative diabetic retinopathy; SNPs: Single nucleotide polymorphisms; IVW-MR: Inverse-variance-weighted mendelian randomization. SMR: Summary-data-based Mendelian randomization
Fig. 2
Fig. 2
Flowchart presenting the process of participants screening in cross-sectional study. DM: Diabetes mellitus; DR: Diabetic retinopathy
Fig. 3
Fig. 3
The forest plot existing causal effect of HMGCR expression on DR. HMGCR: 3-hydroxy-3-methylglutaryl-coenzyme A reductase; IVW (FE): Fixed effects inverse-variance-weighted model; SMR: Summary-data-based mendelian randomization; DR: Diabetic retinopathy; NPDR: Non-proliferative diabetic retinopathy; PDR: Proliferative diabetic retinopathy
See this image and copyright information in PMC

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