Evaluating lipid-lowering drug targets for full-course diabetic retinopathy

作者：Jiahui Cao, Ting Su, Shuilian Chen, Zijing Du, Chunran Lai, Kaiyi Chi, Qin‐Yi Li, Shan Wang, Qiaowei Wu, Yunyan Hu, Ying Fang, Yijun Hu, Zhuoting Zhu, Yu Huang, Xiayin Zhang, Honghua Yu · 发表于：British Journal of Ophthalmology · 年份：2025 · DOI：10.1136/bjo-2024-325771 · 被引用次数：6 · 研究领域：Peroxisome Proliferator-Activated Receptors、Retinal Diseases and Treatments、Genetic Associations and Epidemiology

BACKGROUND: Implementing lipid control in patients with diabetes is regarded as a potential strategy for halting the advancement of diabetic retinopathy (DR). This study seeks to use Mendelian randomisation (MR) to assess the causal relationship between lipid traits and lipid-lowering drug targets and full-course DR (background DR, severe non-proliferative DR (NPDR) and proliferative DR (PDR)). METHODS: A two-sample MR and drug target MR to decipher the causal effects of lipid traits and lipid-lowering drug targets on full-course DR, including background DR, severe NPDR and PDR, was conducted in the study. Genetic variants associated with lipid traits and genes encoding the protein targets of lipid-lowering drugs were extracted from the Global Lipids Genetics Consortium and UK Biobank. Summary-level data of full-course DR are obtained from FinnGen. RESULTS: No significant causal relationship was found between lipid traits and full-course DR. However, in drug target MR analysis, peroxisome proliferator-activated receptor gamma (PPARG) enhancement was associated with lower risks of background DR (OR=0.12, p=0.005) and PDR (OR=0.25, p=0.006). Additionally, mediation MR analysis showed that lowering fasting insulin (p=0.015) and HbA1c (p=0.005) levels mediated most of the association between PPARG and full-course DR. CONCLUSIONS: This study reveals PPARG may be a promising drug target for full-course DR. The activation of PPARG could reduce the risk of full-course DR, especially ...