Evidence map›Paper›PMID 39090671›Full record

ArticleLipids in health and disease2024

Exploring the causal effect between lipid-modifying drugs and idiopathic pulmonary fibrosis: a drug-target Mendelian randomization study.

Gexiang Cai, Jingjing Liu, Mengsi Cai, Lianyou Shao

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Article in Lipids in health and disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

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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

4 authors.

Gexiang CaiDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Jingjing LiuDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Mengsi CaiDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Lianyou ShaoDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. Slyou1994@163.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIdiopathic pulmonary fibrosis (IPF) is a respiratory disorder of obscure etiology and limited treatment options, possibly linked to dysregulation in lipid metabolism. While several observational studies suggest that lipid-lowering agents may decrease the risk of IPF, the evidence is inconsistent. The present Mendelian randomization (MR) study aims to determine the association between circulating lipid traits and IPF and to assess the potential influence of lipid-modifying medications for IPF.

methodsSummary statistics of 5 lipid traits (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, apolipoprotein A, and apolipoprotein B) and IPF were sourced from the UK Biobank and FinnGen Project Round 10. The study's focus on lipid-regulatory genes encompassed PCSK9, NPC1L1, ABCG5, ABCG8, HMGCR, APOB, LDLR, CETP, ANGPTL3, APOC3, LPL, and PPARA. The primary effect estimates were determined using the inverse-variance-weighted method, with additional analyses employing the contamination mixture method, robust adjusted profile score, the weighted median, weighted mode methods, and MR-Egger. Summary-data-based Mendelian randomization (SMR) was used to confirm significant lipid-modifying drug targets, leveraging data on expressed quantitative trait loci in relevant tissues. Sensitivity analyses included assessments of heterogeneity, horizontal pleiotropy, and leave-one-out methods.

resultsThere was no significant effect of blood lipid traits on IPF risk (all P＞0.05). Drug-target MR analysis indicated that genetic mimicry for inhibitor of NPC1L1, PCSK9, ABCG5, ABCG8, and APOC3 were associated with increased IPF risks, with odds ratios (ORs) and 95% confidence intervals (CIs) as follows: 2.74 (1.05-7.12, P = 0.039), 1.36 (1.02-1.82, P = 0.037), 1.66 (1.12-2.45, P = 0.011), 1.68 (1.14-2.48, P = 0.009), and 1.42 (1.20-1.67, P = 3.17×10

conclusionsSerum lipid traits did not significantly affect the risk of idiopathic pulmonary fibrosis. Drug targets MR studies examining 12 lipid-modifying drugs indicated that PCSK9 inhibitors could dramatically increase IPF risk, a mechanism that may differ from their lipid-lowering actions and thus warrants further investigation.

Indexed as

Cholesterol, HDLCholesterol, LDLIdiopathic Pulmonary FibrosisMendelian Randomization AnalysisProprotein Convertase 9TriglyceridesAngiopoietin-Like Protein 3Angiopoietin-like ProteinsApolipoprotein B-100Apolipoprotein C-IIIApolipoproteins BATP Binding Cassette Transporter, Subfamily G, Member 5ATP Binding Cassette Transporter, Subfamily G, Member 8Cholesterol Ester Transfer ProteinsFemaleHumansAngiopoietin-Like Protein 3Angiopoietin-like ProteinsANGPTL3 protein, humanAPOB protein, humanAPOC3 protein, humanApolipoprotein B-100Apolipoprotein C-IIIApolipoproteins BATP Binding Cassette Transporter, Subfamily G, Member 5ATP Binding Cassette Transporter, Subfamily G, Member 8CETP protein, humanCholesterol Ester Transfer ProteinsCholesterol, HDLCholesterol, LDLHMGCR protein, humanHydroxymethylglutaryl CoA ReductasesHypolipidemic AgentsLDLR protein, humanLipoprotein LipaseLPL protein, humanMembrane Transport ProteinsNPC1L1 protein, humanPCSK9 protein, humanProprotein Convertase 9Receptors, LDLTriglyceridesDrug-target Mendelian randomizationIdiopathic pulmonary fibrosisLipidsPCSK9Summary-data-based Mendelian randomization

Identifiers

PMID39090671
PMCPMC11293199

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.