PDF(Pubmed)
Abstract：
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.
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.
摘要：
背景：SLCO1B1在介导包括他汀类药物在内的许多不同药物的肝清除中起重要作用，血管紧张素转换酶抑制剂，化疗药物和抗生素。SLCO1B1中的几种变体已被证明具有临床上的显着影响，与这些药物的疗效有关。本研究全面概述了沙特个体的SLCO1B1变异，中东最大的阿拉伯人口之一。
方法：11,889（9,961个外显子组和1,928个药物遗传学基因组）沙特国民的数据集，用于确定SLCO1B1变体的存在和频率，如临床药物遗传学实施联盟(CPIC)所述。
结果：我们确定了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%）]预测临床可操作。等位基因复型向表型转化显示41个OATP1B1复型。我们估计稀有的负担，和新的预测有害变异，由于17个这样的改变。
结论：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SLCO1B1变体的最全面的概述，以及该种族随后的OATP1B1活动，到目前为止，在可用的国际基因组数据库中仍然相对不足。我们认为，所提供的数据为进一步的临床研究和个性化他汀类药物治疗指导在阿拉伯人中的应用提供了基础。
方法：11,889（9,961个外显子组和1,928个药物遗传学基因组）沙特国民的数据集，用于确定SLCO1B1变体的存在和频率，如临床药物遗传学实施联盟(CPIC)所述。
结果：我们确定了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%）]预测临床可操作。等位基因复型向表型转化显示41个OATP1B1复型。我们估计稀有的负担，和新的预测有害变异，由于17个这样的改变。
结论：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SLCO1B1变体的最全面的概述，以及该种族随后的OATP1B1活动，到目前为止，在可用的国际基因组数据库中仍然相对不足。我们认为，所提供的数据为进一步的临床研究和个性化他汀类药物治疗指导在阿拉伯人中的应用提供了基础。
