Genetic association of lipid-lowering drugs with aortic aneurysms: a Mendelian randomization study

Gao, Xiong1; Luo, Wei1; Qu, Liyuan2,3,4; Yang, Miaomiao1; Chen, Siyu1; Lei, Li; Yan, Shaohua1; Liang, Hongbin1; Zhang, Xinlu1; Xiao, Min1; Liao, Yulin1; Lee, Alex Pui-Wai5,6; Zhou, Zhongjiang1; Chen, Jiejian7; Zhang, Qiuxia1; Wang, Yuegang1; Xiu, Jiancheng1

2024-02-01

10.1093/eurjpc/zwae044

EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY   影响因子和分区

2047-4873

2047-4881

["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.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 x 10-03) and larger lumen size (aortic maximum area: OR = 1.28, 95% CI = 1.13-1.46, P = 1.48 x 10-04; aortic minimum area: OR = 1.26, 95% CI = 1.21-1.42, P = 1.78 x 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 x 10-03; CETP: OR = 1.38, 95% CI = 1.06-1.80, P = 1.47 x 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.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.Lay summary This Mendelian randomization study used publicly available data involving over 1 million individuals to demonstrate the causal relationship between five target genes of LDL-C-lowering medicines and the risk of aortic aneurysms, and implied one lipid-lowering drug may link with the lumen size of aortic aneurysms.","Graphical Abstract"]

Aortic aneurysms Lipid-lowering drugs Mendelian randomization Genetic instruments Causal relationship

SCI

英语

其他

Cardiovascular System & Cardiology

Cardiac & Cardiovascular Systems

WOS:001163465700001

OXFORD UNIV PRESS

Web of Science

1.Southern Med Univ, Nanfang Hosp, Dept Cardiovasc Surg, 1838 Guangzhou Ave North, Guangzhou 510515, Guangdong, Peoples R China
2.Boluo Cty Peoples Hosp, Dept Endocrinol, 1 Kangbo West Rd,Luoyang St, Huizhou, Guangdong, Peoples R China
3.Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, Dept Cardiol, 1017 Dongmen North Rd, Shenzhen, Guangdong, Peoples R China
4.Southern Univ Sci & Technol, Affiliated Hosp 1, 1017 Dongmen North Rd, Shenzhen, Guangdong, Peoples R China
5.Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Div Cardiol,Shatin, Hong Kong, Peoples R China
6.Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Fac Med, Lab Cardiac Imaging & 3D Printing,Shatin, Hong Kong, Peoples R China
7.South China Univ Technol, Guangzhou Peoples Hosp 1, Sch Med, Dept Med Oncol, 1 Panfu Rd, Guangzhou, Guangdong, Peoples R China

Gao, Xiong,Luo, Wei,Qu, Liyuan,et al. Genetic association of lipid-lowering drugs with aortic aneurysms: a Mendelian randomization study[J]. EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY,2024.

Gao, Xiong.,Luo, Wei.,Qu, Liyuan.,Yang, Miaomiao.,Chen, Siyu.,...&Xiu, Jiancheng.(2024).Genetic association of lipid-lowering drugs with aortic aneurysms: a Mendelian randomization study.EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY.

Gao, Xiong,et al."Genetic association of lipid-lowering drugs with aortic aneurysms: a Mendelian randomization study".EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY (2024).