Associations between four polymorphisms of the SLCO1B1 and effectiveness of the statins: a meta-analysis.

IF 1.7 3区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pharmacogenetics and genomics Pub Date : 2023-06-01 DOI:10.1097/FPC.0000000000000490
Hong Ha Nguyen, Cuc Thi Thu Nguyen, Tran Ngoc Phuong Mai, Phung Thanh Huong
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Abstract

Objective: Statins are the first-choice therapy for dyslipidemia, but their effectiveness can be influenced by genetic polymorphisms. This study was conducted to assess the association of variants of the solute carrier anion transporter family 1B1 (SLCO1B1) gene, which encodes a transporter involving the hepatic clearance of the statins and their therapeutic efficacy.

Method: A systematic review was performed on four electronic databases to identify relevant studies. The pooled mean difference with 95% confidence interval (CI) in percentage change of concentration of LDL-C, total cholesterol (TC), HDL-C, and triglycerides was calculated. Heterogeneity between studies and publication bias, subgroup analyses, and sensitivity analyses were also carried out using R software.

Results: Twenty-one studies on 24 365 participants and four variants [rs4149056 (c.521T>C), rs2306283 (c.388A>G), rs11045819 (c.463C>A), rs4363657 (g.89595T>C)] were analyzed. A statistically significant association was found between the LDL-C-lowering effectiveness and the rs4149056 and rs11045819 in the heterozygote model; and the rs4149056, rs2306283, and rs11045819 in the homozygote model. In the subgroup analyses, non-Asian populations, simvastatin, and pravastatin showed significant associations between LDL-C-lowering efficacy and the rs4149056 or rs2306283. Significant associations between the rs2306283 and HDL-C-increasing effectiveness were found in the homozygote model. Regarding TC-reducing, significant associations were observed in the heterozygote and homozygote models of the rs11045819. There was no heterogeneity and publication bias among most studies.

Conclusion: SLCO1B1 variants can be used as signals to predict the statins' effectiveness.

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四种SLCO1B1多态性与他汀类药物有效性之间的关联:一项荟萃分析。
目的:他汀类药物是治疗血脂异常的首选药物,但其疗效可能受到遗传多态性的影响。本研究旨在评估溶质阴离子转运蛋白家族1B1 (SLCO1B1)基因变异的相关性,该基因编码一种转运蛋白,参与他汀类药物的肝脏清除及其治疗效果。方法:对四个电子数据库进行系统回顾,找出相关研究。计算LDL-C、总胆固醇(TC)、HDL-C和甘油三酯浓度百分比变化的95%置信区间(CI)的合并平均差值。研究之间的异质性、发表偏倚、亚组分析和敏感性分析也使用R软件进行。结果:共分析了21项研究共24 365名参与者和4个变异[rs4149056 (C . 521t >C)、rs2306283 (C . 388a >G)、rs11045819 (C . 463c >A)、rs4363657 (G . 89595t >C)]。在杂合子模型中,rs4149056和rs11045819降低ldl - c的有效性与rs4149056和rs11045819存在显著的统计学相关性;纯合子模型中的rs4149056、rs2306283和rs11045819。在亚组分析中,非亚洲人群、辛伐他汀和普伐他汀显示降低ldl - c的疗效与rs4149056或rs2306283之间存在显著关联。在纯合子模型中发现rs2306283与hdl - c增加有效性之间存在显著关联。关于tc降低,在rs11045819的杂合子和纯合子模型中观察到显著的关联。大多数研究不存在异质性和发表偏倚。结论:SLCO1B1变异可作为预测他汀类药物疗效的信号。
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来源期刊
Pharmacogenetics and genomics
Pharmacogenetics and genomics 医学-生物工程与应用微生物
CiteScore
3.20
自引率
3.80%
发文量
47
审稿时长
3 months
期刊介绍: ​​​​Pharmacogenetics and Genomics is devoted to the rapid publication of research papers, brief review articles and short communications on genetic determinants in response to drugs and other chemicals in humans and animals. The Journal brings together papers from the entire spectrum of biomedical research and science, including biochemistry, bioinformatics, clinical pharmacology, clinical pharmacy, epidemiology, genetics, genomics, molecular biology, pharmacology, pharmaceutical sciences, and toxicology. Under a single cover, the Journal provides a forum for all aspects of the genetics and genomics of host response to exogenous chemicals: from the gene to the clinic.
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