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Genetic association of lipid-lowering drugs with aortic aneurysms: a Mendelian randomization study.
- Source :
-
European journal of preventive cardiology [Eur J Prev Cardiol] 2024 Jul 23; Vol. 31 (9), pp. 1132-1140. - Publication Year :
- 2024
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Abstract
- Aims: The lack of effective pharmacotherapies for aortic aneurysms (AA) is a persistent clinical challenge. Lipid metabolism plays an essential role in AA. However, the impact of lipid-lowering drugs on AA remains controversial. The study aimed to investigate the genetic association between lipid-lowering drugs and AA.<br />Methods and Results: Our research used publicly available data on genome-wide association studies (GWASs) and expression quantitative trait loci (eQTL) studies. Genetic instruments, specifically eQTLs related to drug-target genes and SNPs (single nucleotide polymorphisms) located near or within the drug-target loci associated with low-density lipoprotein cholesterol (LDL-C), have been served as proxies for lipid-lowering medications. Drug-Target Mendelian Randomization (MR) study is used to determine the causal association between lipid-lowering drugs and different types of AA. The MR analysis revealed that higher expression of HMGCR (3-hydroxy-3-methylglutaryl coenzyme A reductase) was associated with increased risk of AA (OR = 1.58, 95% CI = 1.20-2.09, P = 1.20 × 10-03) and larger lumen size (aortic maximum area: OR = 1.28, 95% CI = 1.13-1.46, P = 1.48 × 10-04; aortic minimum area: OR = 1.26, 95% CI = 1.21-1.42, P = 1.78 × 10-04). PCSK9 (proprotein convertase subtilisin/kexin type 9) and CETP (cholesteryl ester transfer protein) show a suggestive relationship with AA (PCSK9: OR = 1.34, 95% CI = 1.10-1.63, P = 3.07 × 10-03; CETP: OR = 1.38, 95% CI = 1.06-1.80, P = 1.47 × 10-02). No evidence to support genetically mediated NPC1L1 (Niemann-Pick C1-Like 1) and LDLR (low-density lipoprotein cholesterol receptor) are associated with AA.<br />Conclusion: This study provides causal evidence for the genetic association between lipid-lowering drugs and AA. Higher gene expression of HMGCR, PCSK9, and CETP increases AA risk. Furthermore, HMGCR inhibitors may link with smaller aortic lumen size.<br />Competing Interests: Conflict of interest: none declared.<br /> (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)
- Subjects :
- Humans
Aortic Aneurysm genetics
Aortic Aneurysm epidemiology
Quantitative Trait Loci
Hypolipidemic Agents therapeutic use
Risk Factors
Genetic Predisposition to Disease
Risk Assessment
Phenotype
Dyslipidemias genetics
Dyslipidemias drug therapy
Dyslipidemias blood
Dyslipidemias epidemiology
Receptors, LDL genetics
Pharmacogenomic Variants
Cholesterol, LDL blood
Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use
Mendelian Randomization Analysis
Polymorphism, Single Nucleotide
Genome-Wide Association Study
Cholesterol Ester Transfer Proteins genetics
Proprotein Convertase 9 genetics
Hydroxymethylglutaryl CoA Reductases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2047-4881
- Volume :
- 31
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- European journal of preventive cardiology
- Publication Type :
- Academic Journal
- Accession number :
- 38302118
- Full Text :
- https://doi.org/10.1093/eurjpc/zwae044