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Pharmacogenomics landscape of COVID-19 therapy response in Serbian population and comparison with worldwide populations.
Journal of Medical Biochemistry ( IF 2.5 ) Pub Date : 2020-10-02 , DOI: 10.5937/jomb0-26725
Biljana Stanković 1 , Nikola Kotur 1 , Vladimir Gašić 1 , Kristel Klaassen 1 , Bojan Ristivojević 1 , Maja Stojiljković 1 , Sonja Pavlović 1 , Branka Zukić 1
Affiliation  

BACKGROUND Since there are no certified therapeutics to treat COVID-19 patients, drug repurposing became important. With lack of time to test individual pharmacogenomics markers, population pharmacogenomics could be helpful in predicting a higher risk of developing adverse reactions and treatment failure in COVID-19 patients. Aim of our study was to identify pharmacogenes and pharmacogenomics markers associated with drugs recommended for COVID-19 treatment, chloroquine/hydroxychloroquine, azithromycin, lopinavir and ritonavir, in population of Serbia and other world populations. METHODS Genotype information of 143 individuals of Serbian origin was extracted from database previously obtained using TruSight One Gene Panel (Illumina). Genotype data of individuals from different world populations were extracted from the 1000 Genome Project. Fisher's exact test was used for comparison of allele frequencies. RESULTS We have identified 11 potential pharmacogenomics markers in 7 pharmacogenes relevant for COVID-19 treatment. Based on high alternative allele frequencies in population and the functional effect of the variants, ABCB1 rs1045642 and rs2032582 could be relevant for reduced clearance of azithromycin, lopinavir and ritonavir drugs and UGT1A7 rs17868323 for hyperbilirubinemia in ritonavir treated COVID-19 patients in Serbian population. SLCO1B1 rs4149056 is a potential marker of lopinavir response, especially in Italian population. Our results confirmed that pharmacogenomics profile of African population is different from the rest of the world. CONCLUSIONS Considering population specific pharmacogenomics landscape, preemptive testing for pharmacogenes relevant for drugs used in COVID-19 treatment could contribute to better understanding of the inconsistency in therapy response and could be applied to improve the outcome of the COVID-19 patients.

中文翻译:

塞尔维亚人群 COVID-19 治疗反应的药物基因组学概况以及与全球人群的比较。

背景 由于没有经过认证的疗法来治疗 COVID-19 患者,因此药物再利用变得很重要。由于没有时间测试个体药物基因组学标记物,群体药物基因组学可能有助于预测 COVID-19 患者发生不良反应和治疗失败的更高风险。我们研究的目的是在塞尔维亚和其他世界人口中确定与推荐用于 COVID-19 治疗的药物、氯喹/羟氯喹、阿奇霉素、洛匹那韦和利托那韦相关的药物基因组学和药物基因组学标记物。方法 从先前使用 TruSight One Gene Panel (Illumina) 获得的数据库中提取 143 个塞尔维亚人的基因型信息。来自不同世界人口的个体的基因型数据是从 1000 基因组计划中提取的。Fisher 精确检验用于等位基因频率的比较。结果 我们在与 COVID-19 治疗相关的 7 种药物基因中鉴定了 11 种潜在的药物基因组学标记。基于人群中较高的替代等位基因频率和变异的功能效应,ABCB1 rs1045642 和 rs2032582 可能与阿奇霉素、洛匹那韦和利托那韦药物的清除率降低有关,而 UGT1A7 rs17868323 可能与利托那韦治疗的塞尔维亚人群中 COVID-19 患者的高胆红素血症有关。SLCO1B1 rs4149056 是洛匹那韦反应的潜在标志物,尤其是在意大利人群中。我们的结果证实,非洲人口的药物基因组学概况与世界其他地区不同。结论 考虑到特定人群的药物基因组学景观,
更新日期:2020-10-02
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