Genetic association analysis of lipid-lowering drug target genes in chronic kidney disease DOI Creative Commons
Yi Zhang,

Guangyang Ou,

Peng Lei

et al.

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 14, 2025

The impact of lipid-lowering medications on chronic kidney disease (CKD) remains a subject debate. This Mendelian randomization (MR) study aims to elucidate the potential effects drug targets CKD development. We extracted 11 genetic variants encoding drugs from published genome-wide association (GWAS) summary statistics, encompassing LDLR, HMGCR, PCSK9, NPC1L1, APOB, ABCG5/ABCG8, LPL, APOC3, ANGPTL3, and PPARA. A analysis was conducted targeting these drug-related genes. risk designated as primary outcome, while estimated glomerular filtration rate (eGFR) blood urea nitrogen (BUN) were assessed secondary outcomes. Additionally, mediation performed utilizing 731 immune cell phenotypes identify mediators. meta-analysis revealed significant between ANGPTL3 inhibitors reduced (OR [95% CI] = 0.85 [0.75-0.96]). Conversely, LDLR agonists significantly linked an increased 1.11 [1.02-1.22]). Regarding outcomes, did not affect eGFR BUN levels. Mediation indicated that reduction in by mediated through modulation phenotype, specifically HLA-DR CD14+ CD16+ monocytes (Mediated proportion: 4.69%; Mediated effect: -0.00899). Through drug-targeted MR analysis, we identified causal relationship CKD. may represent promising candidate for treatment.

Language: Английский

Genetic association analysis of lipid-lowering drug target genes in chronic kidney disease DOI Creative Commons
Yi Zhang,

Guangyang Ou,

Peng Lei

et al.

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 14, 2025

The impact of lipid-lowering medications on chronic kidney disease (CKD) remains a subject debate. This Mendelian randomization (MR) study aims to elucidate the potential effects drug targets CKD development. We extracted 11 genetic variants encoding drugs from published genome-wide association (GWAS) summary statistics, encompassing LDLR, HMGCR, PCSK9, NPC1L1, APOB, ABCG5/ABCG8, LPL, APOC3, ANGPTL3, and PPARA. A analysis was conducted targeting these drug-related genes. risk designated as primary outcome, while estimated glomerular filtration rate (eGFR) blood urea nitrogen (BUN) were assessed secondary outcomes. Additionally, mediation performed utilizing 731 immune cell phenotypes identify mediators. meta-analysis revealed significant between ANGPTL3 inhibitors reduced (OR [95% CI] = 0.85 [0.75-0.96]). Conversely, LDLR agonists significantly linked an increased 1.11 [1.02-1.22]). Regarding outcomes, did not affect eGFR BUN levels. Mediation indicated that reduction in by mediated through modulation phenotype, specifically HLA-DR CD14+ CD16+ monocytes (Mediated proportion: 4.69%; Mediated effect: -0.00899). Through drug-targeted MR analysis, we identified causal relationship CKD. may represent promising candidate for treatment.

Language: Английский

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