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. 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). 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. 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.

中文翻译：

---

基于大规模下一代测序的沙特人群 SLCO1B1 药物遗传学变异分析

SLCO1B1 在介导许多不同药物的肝脏清除中发挥重要作用，包括他汀类药物、血管紧张素转换酶抑制剂、化疗药物和抗生素。 SLCO1B1 的几种变异已被证明对这些药物的疗效具有临床显着影响。这项研究全面概述了沙特个体的 SLCO1B1 变异，沙特阿拉伯是中东最大的阿拉伯人口之一。根据临床药物遗传学实施联盟 (CPIC) 的描述，11,889 名沙特国民（9,961 个外显子组和 1,928 个药物遗传学基因组）的数据集用于确定 SLCO1B1 变异的存在和频率。我们鉴定了 141 个先前描述的 SNP，其中 rs2306283 (50%) 和 rs4149056 (28%) 是最常见的。此外，我们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%) ]预计在临床上是可行的。等位基因双倍型到表型的转换揭示了 41 个 OATP1B1 双倍型。我们估计了由 17 个此类改变引起的罕见且新颖的预测有害变异的负担。我们提供的数据来自迄今为止研究的最大的阿拉伯群体之一，提供了该族群 SLCO1B1 变体以及随后的 OATP1B1 活性的最全面的概述，迄今为止，该族群在可用的国际基因组数据库中的代表性仍然相对不足。我们相信，所提供的数据为阿拉伯人的进一步临床研究和个性化他汀类药物治疗指导的应用提供了基础。