利用药物基因组学数据在阿联酋人中更安全地使用他汀类药物。

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Applied Bio Materials Pub Date : 2024-01-01 DOI:10.2174/0115701611283841231227064343
Mais N Alqasrawi, Zeina N Al-Mahayri, Hiba Alblooshi, Habiba Alsafar, Bassam R Ali
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引用次数: 0

摘要

背景:他汀类药物是全球处方量最大的降脂药物。尽管他汀类药物具有一定的安全性,但与之相关的不良反应,尤其是肌肉症状却屡见报端。溶质载体有机阴离子转运体家族成员 1B1 (SLCO1B1)、ATP 结合盒 G 亚家族成员 2 (ABCG2) 和细胞色素 P450 9C9 (CYP2C9) 这三种药物基因被认为是他汀类药物的安全性生物标志物。临床药理基因组实施联盟(CPIC)根据这三个基因发布了他汀类药物使用的临床指南:本研究旨在检测这些药物基因的变异,以预测阿联酋人群使用他汀类药物的安全性:方法:分析这三个基因的 242 个全外显子组测序数据,确定单核苷酸多态性 (SNP) 的频率,注释单倍型及其蛋白质的预测功能:在我们的队列中,分别有 29.8% 和 5.4% 的人 SLCO1B1 功能减退和功能低下。这一高频率警示我们某些他汀类药物可能会产生重大副作用,以及药物基因组学检测的重要性。我们发现,ABCG2:rs2231142变异的频率较低(6%),这表明与该变异频率较高的其他人群相比,阿联酋患者被建议服用较高剂量罗伐他汀的可能性较低。与此相反,我们发现功能受损的 CYP2C9 等位基因的频率较高,这使得氟伐他汀成为一个不太有利的选择:结论:在现有的稀少研究中,本研究显示了阿联酋人中所有的SLCO1B1和CYP2C9功能受损等位基因。我们强调了特定人群的药物基因组数据如何能够预测他汀类药物的更安全选择,尤其是在研究不足的人群中。
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Utilizing Pharmacogenomic Data for a Safer Use of Statins among the Emirati Population.

Background: Statins are the most prescribed lipid-lowering drugs worldwide. The associated adverse events, especially muscle symptoms, have been frequently reported despite their perceived safety. Three pharmacogenes, the solute carrier organic anion transporter family member 1B1 (SLCO1B1), ATP-binding cassette subfamily G member 2 (ABCG2), and cytochrome P450 2C9 (CYP2C9) are suggested as safety biomarkers for statins. The Clinical Pharmacogenomic Implementation Consortium (CPIC) issued clinical guidelines for statin use based on these three genes.

Objectives: The present study aimed to examine variants in these pharmacogenes to predict the safety of statin use among the Emirati population.

Methods: Analyzing 242 whole exome sequencing data at the three genes enabled the determination of the frequencies of the single nucleotide polymorphisms (SNPs), annotating the haplotypes and the predicted functions of their proteins.

Results: In our cohort, 29.8% and 5.4% had SLCO1B1 decreased and poor function, respectively. The high frequency warns of the possibility of significant side effects of some statins and the importance of pharmacogenomic testing. We found a low frequency (6%) of the ABCG2:rs2231142 variant, which indicates the low probability of Emirati patients being recommended against higher rosuvastatin doses compared with other populations with higher frequencies of this variant. In contrast, we found high frequencies of the functionally impaired CYP2C9 alleles, which makes fluvastatin a less favorable choice.

Conclusion: Among the sparse studies available, the present one demonstrates all SLCO1B1 and CYP2C9 function-impairing alleles among Emiratis. We highlighted how population-specific pharmacogenomic data can predict safer choices of statins, especially in understudied populations.

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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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