基于新一代测序技术的大规模沙特人群 SLCO1B1 药物遗传学变异分析。

IF 3.8 3区 医学 Q2 GENETICS & HEREDITY
Ewa Goljan, Mohammed Abouelhoda, Asma Tahir, Mohamed ElKalioby, Brian Meyer, Dorota Monies
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引用次数: 0

摘要

背景:SLCO1B1 在介导他汀类药物、血管紧张素转换酶抑制剂、化疗药物和抗生素等多种不同药物的肝清除过程中发挥着重要作用。研究表明,SLCO1B1 中的几种变异对这些药物的疗效有显著的临床影响。本研究全面概述了中东地区最大的阿拉伯人口之一--沙特人的 SLCO1B1 变异情况:方法:根据临床药理基因实施联盟(CPIC)的描述,使用 11,889 个沙特人(961 个外显子组和 1928 个药物基因组)的数据集来确定 SLCO1B1 变异的存在和频率:结果:我们发现了 141 个先前描述过的 SNPs,其中 rs2306283(50%)和 rs4149056(28%)最为常见。此外,我们还观察到六个等位基因[*15(24.7%),其次是*20(8.04%)、*14(5.86%)、*5(3.84%)、*31(0.21%)和*9(0.03%)],预测这些等位基因可用于临床。从等位基因二联型到表型的转换显示了 41 种 OATP1B1 二联型。我们估算了由 17 个此类变异导致的罕见和新型预测有害变异的负担:我们所提供的数据来自迄今为止所研究的最大的阿拉伯队列之一,这些数据最全面地概述了 SLCO1B1 变异以及该族群随后的 OATP1B1 活性,迄今为止,该族群在现有国际基因组数据库中的代表性仍然相对不足。我们相信,所提供的数据为进一步的临床研究和在阿拉伯人中应用个性化他汀类药物治疗指导奠定了基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Large-scale next generation sequencing based analysis of SLCO1B1 pharmacogenetics variants in the Saudi population.

Background: SLCO1B1 plays an important role in mediating hepatic clearance of many different drugs including statins, angiotensin-converting enzyme inhibitors, chemotherapeutic agents and antibiotics. Several variants in SLCO1B1 have been shown to have a clinically significant impact, in relation to efficacy of these medications. This study provides a comprehensive overview of SLCO1B1 variation in Saudi individuals, one of the largest Arab populations in the Middle East.

Methods: The dataset of 11,889 (9,961 exomes and 1,928 pharmacogenetic gene panel) Saudi nationals, was used to determine the presence and frequencies of SLCO1B1 variants, as described by the Clinical Pharmacogenetic Implementation Consortium (CPIC).

Results: We identified 141 previously described SNPs, of which rs2306283 (50%) and rs4149056 (28%), were the most common. In addition, we observed six alleles [*15 (24.7%) followed by *20 (8.04%), *14 (5.86%), *5 (3.84%), *31 (0.21%) and *9 (0.03%)] predicted to be clinically actionable. Allele diplotype to phenotype conversion revealed 41 OATP1B1 diplotypes. We estimated the burden of rare, and novel predicted deleterious variants, resulting from 17 such alterations.

Conclusions: The data we present, from one of the largest Arab cohorts studied to date, provides the most comprehensive overview of SLCO1B1 variants, and the subsequent OATP1B1 activity of this ethnic group, which thus far remains relatively underrepresented in available international genomic databases. We believe that the presented data provides a basis for further clinical investigations and the application of personalized statin drug therapy guidance in Arabs.

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来源期刊
Human Genomics
Human Genomics GENETICS & HEREDITY-
CiteScore
6.00
自引率
2.20%
发文量
55
审稿时长
11 weeks
期刊介绍: Human Genomics is a peer-reviewed, open access, online journal that focuses on the application of genomic analysis in all aspects of human health and disease, as well as genomic analysis of drug efficacy and safety, and comparative genomics. Topics covered by the journal include, but are not limited to: pharmacogenomics, genome-wide association studies, genome-wide sequencing, exome sequencing, next-generation deep-sequencing, functional genomics, epigenomics, translational genomics, expression profiling, proteomics, bioinformatics, animal models, statistical genetics, genetic epidemiology, human population genetics and comparative genomics.
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