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ABCG2基因多态性与他汀类药物所致不良事件的关联:一项荟萃分析。

Association Between ABCG2 Polymorphism and Statin-Induced Adverse Events: A Meta-Analysis.

作者信息

Lee Da Hoon, Shin Hae Ji, Yoon Beom, Kim Han Wool, Jo Hyeon Woo, Kim Hee Jung, Kim Woorim

机构信息

College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea.

College of Pharmacy, Kangwon National University, 1 Kangwondaehak-gil, Chuncheon-si, Gangwon-do, 24341, Republic of Korea.

出版信息

Cardiovasc Toxicol. 2025 Aug 23. doi: 10.1007/s12012-025-10056-w.

DOI:10.1007/s12012-025-10056-w
PMID:40848094
Abstract

Statins, widely used for preventing cardiovascular diseases due to their cholesterol-lowering effects, are associated with potential adverse reactions in some individuals, underscoring the need to understand the factors contributing to statin-related complications. The ATP-binding cassette subfamily G member 2 (ABCG2) gene, which encodes a multidrug transporter, has garnered attention due to its involvement in statin metabolism. Specifically, the rs2231142 polymorphism within ABCG2 has been implicated in altered drug metabolism and pharmacokinetics, potentially influencing statin-related toxicity. Despite previous investigations, findings regarding this association remain inconclusive. Thus, this systematic review and meta-analysis aimed to clarify the correlation between the rs2231142 polymorphism and statin-induced toxicity. Through a comprehensive literature search, seven eligible studies were identified and subjected to rigorous data extraction and quality assessment. Meta-analysis revealed a significant association between the rs2231142 polymorphism and an increased risk of overall statin-induced toxicity, including muscular and hepatic toxicity, with odds ratios of 2.6 and 2.7, respectively. These findings suggest a potential role for ABCG2 polymorphisms in statin-related adverse events and emphasize the importance of personalized treatment strategies in managing statin therapy.

摘要

他汀类药物因其降胆固醇作用而被广泛用于预防心血管疾病,但在一些个体中与潜在不良反应相关,这凸显了了解导致他汀类药物相关并发症的因素的必要性。编码多药转运蛋白的三磷酸腺苷结合盒亚家族G成员2(ABCG2)基因,因其参与他汀类药物代谢而受到关注。具体而言,ABCG2基因内的rs2231142多态性与药物代谢和药代动力学改变有关,可能影响他汀类药物相关毒性。尽管此前已有研究,但关于这种关联的结果仍无定论。因此,本系统评价和荟萃分析旨在阐明rs2231142多态性与他汀类药物诱导的毒性之间的相关性。通过全面的文献检索,确定了七项符合条件的研究,并对其进行了严格的数据提取和质量评估。荟萃分析显示,rs2231142多态性与他汀类药物诱导的总体毒性风险增加之间存在显著关联,包括肌肉毒性和肝毒性,比值比分别为2.6和2.7。这些发现表明ABCG2多态性在他汀类药物相关不良事件中可能发挥作用,并强调了个性化治疗策略在他汀类药物治疗管理中的重要性。

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本文引用的文献

1
The Benefits Outweigh the Risks of Treating Hypercholesterolemia: The Statin Dilemma.治疗高胆固醇血症利大于弊:他汀类药物困境
Cureus. 2023 Jan 11;15(1):e33648. doi: 10.7759/cureus.33648. eCollection 2023 Jan.
2
Molecular targets of statins and their potential side effects: Not all the glitter is gold.他汀类药物的分子靶点及其潜在副作用:并非所有闪光点都是金子。
Eur J Pharmacol. 2022 May 5;922:174906. doi: 10.1016/j.ejphar.2022.174906. Epub 2022 Mar 20.
3
Hydrophilic or Lipophilic Statins?亲水性还是亲脂性他汀类药物?
Front Cardiovasc Med. 2021 May 20;8:687585. doi: 10.3389/fcvm.2021.687585. eCollection 2021.
4
Effects of statins on mitochondrial pathways.他汀类药物对线粒体途径的影响。
J Cachexia Sarcopenia Muscle. 2021 Apr;12(2):237-251. doi: 10.1002/jcsm.12654. Epub 2021 Jan 29.
5
Pharmacogenetics of Statin-Induced Myotoxicity.他汀类药物所致肌毒性的药物遗传学
Front Genet. 2020 Oct 16;11:575678. doi: 10.3389/fgene.2020.575678. eCollection 2020.
6
Genetic and Clinical Factors Are Associated With Statin-Related Myotoxicity of Moderate Severity: A Case-Control Study.遗传和临床因素与中等严重程度的他汀类药物相关肌毒性相关:一项病例对照研究。
Clin Pharmacol Ther. 2018 Jul;104(1):178-187. doi: 10.1002/cpt.887. Epub 2017 Nov 9.
7
Pharmacogenomics of Rosuvastatin: A Glocal (Global+Local) African Perspective and Expert Review on a Statin Drug.瑞舒伐他汀的药物基因组学:从全球本土化(全球+本地)非洲视角及对一种他汀类药物的专家评论
OMICS. 2016 Sep;20(9):498-509. doi: 10.1089/omi.2016.0114.
8
ABCG2 gene polymorphisms as risk factors for atorvastatin adverse reactions: a case-control study.ABCG2基因多态性作为阿托伐他汀不良反应的危险因素:一项病例对照研究。
Pharmacogenomics. 2015 Jul;16(8):803-15. doi: 10.2217/pgs.15.47. Epub 2015 Jun 18.
9
Association between statin-induced creatine kinase elevation and genetic polymorphisms in SLCO1B1, ABCB1 and ABCG2.他汀类药物诱导的肌酸激酶升高与SLCO1B1、ABCB1和ABCG2基因多态性之间的关联
Eur J Clin Pharmacol. 2014 May;70(5):539-47. doi: 10.1007/s00228-014-1661-6. Epub 2014 Mar 6.
10
CYP2C9 and ABCG2 polymorphisms as risk factors for developing adverse drug reactions in renal transplant patients taking fluvastatin: a case-control study.CYP2C9 和 ABCG2 多态性与肾移植患者服用氟伐他汀发生不良反应的风险因素相关:一项病例对照研究。
Pharmacogenomics. 2013 Sep;14(12):1419-31. doi: 10.2217/pgs.13.135.