Department of Biopharmaceutics and Clinical Pharmacy, School of Pharmacy, University of Jordan, Amman, Jordan.
Department of Pharmacy, College of Pharmacy, Al-Zaytoonah University of Jordan, Amman, Jordan.
Curr Drug Metab. 2019;20(5):399-410. doi: 10.2174/1389200220666190528085151.
Glucuronidation is one of the most important phase II metabolic pathways. It is catalyzed by a family of UDP-glucuronosyltransferase enzymes (UGTs). UGT1A1 and UGT1A7 catalyze the glucuronidation of a diverse range of medications, environmental chemicals and endogenous compounds. Polymorphisms in the UGT1A gene could potentially be significant for the pharmacological, toxicological and physiological effects of the enzymes.
The UGT1A gene is polymorphic among ethnic groups and the aim of this study was to investigate the different UGT1A1 and UGT1A7 polymorphisms in Circassians, Chechens and Jordanian-Arabs.
A total of 168 healthy Jordanian-Arabs, 56 Circassians and 54 Chechens were included in this study. Genotyping of 20 different Single-nucleotide polymorphism (SNPs) was done by using polymerase chain reaction- DNA sequencing.
We found that Circassians and Chechens have significantly higher allele frequencies of UGT1A72, UGT1A73 and UGT1A74 than the Jordanian-Arab population, but all three populations have similar frequencies of UGT1A128. Therefore, Circassians and Chechens are expected to have significantly lower levels of the UGT1A7 enzyme with almost 90% of these populations having genes that encode low or intermediate enzyme activity.
This inter-ethnic variation in the UGT1A alleles frequencies may affect drug response and susceptibility to cancers among different subethnic groups in Jordan. Our results can also provide useful information for the Jordanian population and for future genotyping of Circassian and Chechen populations in general.
葡萄糖醛酸化是最重要的 II 相代谢途径之一。它由一组 UDP-葡萄糖醛酸基转移酶（UGTs）催化。UGT1A1 和 UGT1A7 催化多种药物、环境化学物质和内源性化合物的葡萄糖醛酸化。UGT1 基因的多态性可能对酶的药理学、毒理学和生理学效应有重要意义。
UGT1 基因在不同种族中存在多态性，本研究旨在研究在克里米亚鞑靼人、车臣人和约旦阿拉伯人之间不同的 UGT1A1 和 UGT1A7 多态性。
本研究共纳入 168 名健康的约旦阿拉伯人、56 名克里米亚鞑靼人和 54 名车臣人。通过聚合酶链反应-DNA 测序对 20 种不同的单核苷酸多态性（SNP）进行基因分型。
我们发现克里米亚鞑靼人和车臣人 UGT1A72、UGT1A73 和 UGT1A74 的等位基因频率明显高于约旦阿拉伯人群，但这三个人群的 UGT1A128 频率相似。因此，克里米亚鞑靼人和车臣人预计 UGT1A7 酶的水平显著降低，几乎 90%的人群具有编码低或中等酶活性的基因。
UGT1A 等位基因频率的这种种族间差异可能会影响约旦不同亚群的药物反应和癌症易感性。我们的结果还可以为约旦人群提供有用的信息，并为克里米亚鞑靼人和车臣人未来的基因分型提供信息。
