Evidence mapPaperPMID 39877840Full record

SynthesisFrontiers in endocrinology2024

Genetic association analysis of lipid-lowering drug target genes in chronic kidney disease.

Yi Zhang, Guangyang Ou, Lei Peng, Jian Pan, Shaohua Zhang, Jianguo Shi

Abstract readMeta-Analysis
In one paragraph

Synthesis in Frontiers in endocrinology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Yi Zhang *Department of Urology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou Medical University, Jinzhou, Liaoning, China.
Guangyang Ou *Department of Cardiology, Hunan University of Chinese Medicine, Changsha, China.
Lei Peng *Motor Robotics Institute (MRI), South China Hospital, Health Science Center, Shenzhen University, Shenzhen, China.
Jian PanMotor Robotics Institute (MRI), South China Hospital, Health Science Center, Shenzhen University, Shenzhen, China.
Shaohua ZhangMotor Robotics Institute (MRI), South China Hospital, Health Science Center, Shenzhen University, Shenzhen, China.
Jianguo ShiDepartment of Urology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou Medical University, Jinzhou, Liaoning, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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

Indexed as

Hypolipidemic AgentsRenal Insufficiency, ChronicAngiopoietin-Like Protein 3Genome-Wide Association StudyHumansMendelian Randomization AnalysisPolymorphism, Single NucleotideAngiopoietin-Like Protein 3ANGPTL3 protein, humanHypolipidemic Agentschronic kidney diseaseestimated glomerular filtration ratelipid-lowering druglipidsMendelian randomization analysis

Identifiers

PMID39877840
PMCPMC11772207

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.