Objective To assess the potential causal relationship between lipid phenotypes mediated by lipid-lowering drug targets(HMGCR,PCSK9 and NPC1L1)and the risk of hypertensive nephropathy.Methods Mendelian randomization(MR)analysis was conducted using summary data from publicly available European ancestry genome-wide association studies(GWAS).Genetic variants associated with low-density lipoprotein cholesterol(LDL-C)were used as instrumental variables based on selected lipid-lowering drug target genes screening tools.Inverse variance weighting was selected as the main MR analysis method,with sensitivity analyses conducted to ensure the robustness of the results.Results Genetically predicted LDL-C levels were associated with a higher risk of hypertensive nephropathy(OR=1.19,95%CI:1.03～1.38,P=0.021).Higher LDL-C levels mediated by HMGCR were positively causally related to increased risk of hypertensive nephropathy(OR=4.08,95%CI:2.86～5.81;P＜0.001).However,LDL-C levels mediated by PCSK9 and NPC1L1 showed no significant association with the risk of hypertensive nephropathy.Cochran's Q test,MR-PRESSO,and MR-Egger intercept tests showed no heterogeneity or horizontal pleiotropy among instrumental variables.Conclusions The findings of this study support the causal relationship between LDL-C mediated by HMGCR and increased risk of hypertensive nephropathy,suggesting potential benefits of statin therapy for hypertensive nephropathy.
关键词
调脂药物/他汀类药物/高血压肾病/孟德尔随机化/全基因组关联研究
Key words
lipid-lowering drugs/statins/hypertensive nephropathy/Mendelian randomization/genome-wide association study
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