Genetics and Bioinformatics Department, Dasman Diabetes Institute, Kuwait City, Kuwait.
Narcotic and Psychotropic Department, Ministry of Interior, Farwaniya, Kuwait.
Sci Rep. 2022 Sep 1;12(1):14858. doi: 10.1038/s41598-022-19318-x.
Organic anion transporting polypeptides (OATP), which are encoded by SLCO genes, participate in the hepatic elimination of drugs and xenobiotics. SLCO1B1 is an important pharmacogenomic gene (encoding OATP1B1) associated with response to the uptake of endogenous compounds, such as statin and bilirubin. Ethnicity of the patient modulates the response to these drugs; the frequency and haplotype data for SLCO1B1 genetic variants in the Arab population is lacking. Therefore, we determined the frequencies of two well-characterized SLCO1B1 single nucleotide polymorphisms (SNP) and haplotypes that affect the OATP1B1 drugs transportation activity in Qatari population. Genotyping data for two SLCO1B1 SNPs (c.388A > G, c.521 T > C) were extracted from whole exome data of 1050 Qatari individuals, who were divided into three ancestry groups, namely Bedouins, Persians/South Asians, and Africans. By way of using Fisher's exact and Chi-square tests, we evaluated the differences in minor allele frequency (MAF) of the two functional SNPs and haplotype frequencies (HF) among the three ancestry groups. The OATP1B1 phenotypes were assigned according to their function by following the guidelines from the Clinical Pharmacogenetics Implementation Consortium for SLCO1B1 and Simvastatin-Induced Myopathy.The MAF of SLCO1B1:c.388A > G was higher compared to that of SLCO1B1:c.521 T > C in the study cohort. It was significantly high in the African ancestry group compared with the other two groups, whereas SLCO1B1:c.521 T > C was significantly low in the African ancestry group compared with the other two groups. The SLCO1B1 *15 haplotype had the highest HF, followed by *1b, *1a, and *5. Only the SLCO1B1 *5 haplotype showed no significant difference in frequency across the three ancestry groups. Furthermore, we observed that the OATP1B1 normal function phenotype accounted for 58% of the Qatari individuals, the intermediate function phenotype accounted for 35% with significant differences across the ancestry groups, and the low function phenotype accounted for 6% of the total Qatari individuals with a higher trend observed in the Bedouin group.The results indicate that the phenotype frequencies of the OATP1B1 intermediate and low function in the Qatari population appear at the higher end of the frequency range seen worldwide. Thus, a pharmacogenetic screening program for SLCO1B1 variants may be necessary for the Qatari population.
有机阴离子转运多肽 (OATP) 由 SLCO 基因编码，参与药物和外源性化合物的肝脏消除。SLCO1B1 是与内源性化合物摄取反应相关的重要药物基因组学基因（编码 OATP1B1），如他汀类药物和胆红素。患者的种族会影响对这些药物的反应；阿拉伯人群中 SLCO1B1 遗传变异的频率和单倍型数据尚不清楚。因此，我们确定了两种特征明确的 SLCO1B1 单核苷酸多态性（SNP）的频率和单倍型，这些 SNP 影响卡塔尔人群中 OATP1B1 药物转运活性。对 1050 名卡塔尔个体的全外显子数据提取了两个 SLCO1B1 SNP（c.388A>G、c.521T>C）的基因分型数据，这些个体分为三个祖裔群体，即贝都因人、波斯人/南亚人和非洲人。通过 Fisher 精确检验和卡方检验，我们评估了三个祖裔群体中两个功能 SNP 的次要等位基因频率（MAF）和单倍型频率（HF）的差异。根据临床药物遗传学实施联盟对 SLCO1B1 和辛伐他汀诱导的肌病的指导方针，根据 OATP1B1 表型进行分配。研究队列中 SLCO1B1:c.388A>G 的 MAF 高于 SLCO1B1:c.521T>C。与其他两个群体相比，非洲裔群体中的 MAF 明显较高，而非洲裔群体中的 SLCO1B1:c.521T>C 明显较低。SLCO1B115 单倍型具有最高的 HF，其次是1b、1a 和5。只有 SLCO1B1*5 单倍型在三个祖裔群体中的频率没有显著差异。此外，我们观察到 OATP1B1 正常功能表型占卡塔尔个体的 58%，中间功能表型占 35%，且在祖裔群体中存在显著差异，低功能表型占卡塔尔个体的 6%，且在贝都因人群中呈现出较高的趋势。结果表明，卡塔尔人群中 OATP1B1 中、低功能表型的频率处于全球范围内观察到的频率范围的较高端。因此，SLCO1B1 变体的药物遗传学筛查计划可能对卡塔尔人群是必要的。
