Department of Applied Biological Sciences, Jordan University of Science and Technology, Irbid 22110, Jordan.
Department of Biotechnology and Genetic Engineering, Jordan University of Science and Technology, Irbid 22110, Jordan.
Curr Drug Metab. 2020;21(4):307-317. doi: 10.2174/1389200221666200505081139.
Differences in individual responses to the same medications remarkably differ among populations. A number of genes that play integral roles in drug responses have been designated as very important pharmacogenes (VIP), as they are responsible for differences in drug safety, efficacy, and adverse drug reactions among certain ethnic groups. Identifying the polymorphic distribution of VIP in a range of ethnic groups will be conducive to population-based personalized medicine.
The aim of the current study is to identify the polymorphic distribution of VIP regarding the Chechen minority group from Jordan and compare their allele frequencies with other populations.
A total of 131 unrelated Chechen individuals from Jordan were randomly recruited for blood collection. Identification of allelic and genotypic frequencies of eleven VIP variants within the genes of interest (ABCB1, VDR and TPMT) was carried out by means of the MassARRAY®System (iPLEX GOLD).
Within ABCB1, we found that the minor allele frequencies of the rs1128503 (A: 0.43), rs2032582 (A: 0.43), rs1045642 (A: 0.43). For VDR, the minor allele frequencies of rs11568820 (T: 0.18), rs1540339 (T: 0.30), rs1544410 (T: 0.41), rs2228570 (T: 0.24), rs3782905 (C: 0.28) and rs7975232 (C: 0.45). Finally, the minor allele frequencies for the TPMT rs1142345 and rs1800460 polymorphisms were found to be (C: 0.02) and (T: 0.01), respectively.
Significant differences in allelic frequencies of eleven ABCB1, VDR and TPMT VIP variants were found between Jordanian Chechens and other populations. In our study, most populations that are similar to Chechens are those from South Asian, European (Finnish) and European, including: Utah residents with Northern and Western European ancestry, Toscani in Italia, Mexican ancestry in Los Angeles and Circassian from Jordan. The level of similarity between Chechens and those populations means that they might have shared high levels of gene flow in the past. The results obtained in this study will contribute to the worldwide pharmacogenomic databases and provide valuable information for future studies and better individualized treatments.
个体对相同药物的反应存在显著差异,这在不同人群中表现得尤为明显。许多在药物反应中发挥重要作用的基因被指定为非常重要的药物基因(VIP),因为它们是导致某些种族群体的药物安全性、疗效和药物不良反应差异的原因。确定一系列种族群体中 VIP 的多态性分布将有利于基于人群的个体化医学。
本研究旨在鉴定来自约旦的车臣少数民族群体中 VIP 的多态性分布,并将其等位基因频率与其他人群进行比较。
从约旦随机招募了 131 名无关的车臣个体进行采血。通过 MassARRAY®系统(iPLEX GOLD)检测目的基因(ABCB1、VDR 和 TPMT)中 11 个 VIP 变异的等位基因和基因型频率。
在 ABCB1 中,我们发现 rs1128503(A:0.43)、rs2032582(A:0.43)和 rs1045642(A:0.43)的次要等位基因频率较低。对于 VDR,rs11568820(T:0.18)、rs1540339(T:0.30)、rs1544410(T:0.41)、rs2228570(T:0.24)、rs3782905(C:0.28)和 rs7975232(C:0.45)的次要等位基因频率较低。最后,TPMT rs1142345 和 rs1800460 多态性的次要等位基因频率分别为(C:0.02)和(T:0.01)。
在约旦车臣人和其他人群之间发现了 11 个 ABCB1、VDR 和 TPMT VIP 变异的等位基因频率存在显著差异。在我们的研究中,与车臣人最相似的大多数人群来自南亚、欧洲(芬兰)和欧洲,包括:犹他州有北西方和西方欧洲血统的居民、意大利的托斯卡纳人、洛杉矶的墨西哥裔和来自约旦的切尔克斯人。车臣人与这些人群之间的相似程度意味着他们过去可能有较高水平的基因流。本研究获得的结果将有助于建立全球药物基因组学数据库,并为未来的研究和更好的个体化治疗提供有价值的信息。