背景:糖尿病视网膜病变(DR)是全球劳动年龄人群视力丧失的首要原因,他汀类药物是DR患者最常用的血脂管理药物之一。他汀类药物与DR之间的确切关系尚未确定。本研究旨在验证他汀类药物使用与糖尿病视网膜病变之间的因果关系。
方法:基于汇总数据的孟德尔随机化(SMR)方法和逆方差加权孟德尔随机化(IVW-MR)用于通过使用3-羟基-3-甲基戊二酰辅酶A还原酶(HMGCR)的表达数量性状基因座(eQTL)数据(31,684个血液)来确定他汀类药物与DR之间的因果关系低密度脂蛋白胆固醇相关GWAS数据(样本量:440,546),和DR相关的GWAS数据(14,584例和176,010例对照)。此外,我们基于国家健康和营养调查(NHANES)的数据进行了一项横断面观察性研究,以补充DR和他汀类药物之间的关联(样本量:106,911).使用具有相应的95%置信区间(CI)的比值比(OR)来评估结果。
结果:根据MR分析结果,HMGCR抑制剂与DR的发病率明显增高有因果关系(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)。亚组分析显示,结果不受DR严重程度的影响。敏感性分析揭示了MR分析结果的稳定性和可靠性。基于NHANES的横断面研究的结果也支持了不服用他汀类药物与DR风险降低之间的关联(OR=0.54,95%CI[0.37,0.79],p=0.001)。
结论:这项研究表明,DR风险的显著增加与他汀类药物的使用有因果关系,为他汀类药物在DR中的作用提供新的见解。然而,需要进一步调查以验证这些发现。
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.
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.
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).
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.