Liu Lijun, Chang Yu, Du Shuli, Shi Xugang, Yang Hua, Kang Longli, Jin Tianbo, Yuan Dongya, He Yongjun
Key Laboratory for Molecular Genetic Mechanisms and Intervention Research on High Altitude Disease of Tibet Autonomous Region, Xizang Minzu University, Xianyang, Shaanxi 712082, People's Republic of China.
J Genet. 2017 Jun;96(2):219-225. doi: 10.1007/s12041-017-0757-z.
The enzymatic activity of CYP3A4 results in broad interindividual variability in response to certain pharmacotherapies. The present study aimed to screen Tibetan volunteers for CYP3A4 genetic polymorphisms. Previous research has focussed on Han Chinese patients, while little is known about the genetic variation of CYP3A4 in the Tibetan populations. Here, we adopted DNA sequencing to investigate the promoter, exons and surrounding introns, and 3'-untranslated region of the CYP3A4 gene in 96 unrelated healthy Tibetan individuals.We identified 20 different CYP3A4 polymorphisms in the Tibetan population, including two novel variants (21824 A>G and 15580 G>C). In addition, we also determined the allele frequencies of CYP3A41A and CYP3A41H were 82.29% and 28.13%, respectively. CYP3A4*1P and *1G were relatively rare with frequencies of only 1.04% and 0.52%, respectively. Our results provide information on CYP3A4 polymorphisms in Tibetan individuals which may help to optimize pharmacotherapy effectiveness by providing personalized medicine to this ethnic group.
CYP3A4的酶活性导致个体对某些药物治疗的反应存在广泛的个体差异。本研究旨在筛查藏族志愿者的CYP3A4基因多态性。以往的研究主要集中在汉族患者，而对藏族人群中CYP3A4的基因变异了解甚少。在此，我们采用DNA测序法对96名无亲缘关系的健康藏族个体的CYP3A4基因启动子、外显子及周围内含子和3'非翻译区进行了研究。我们在藏族人群中鉴定出20种不同的CYP3A4多态性，包括两种新变异（21824 A>G和15580 G>C）。此外，我们还确定了CYP3A41A和CYP3A41H的等位基因频率分别为82.29%和28.13%。CYP3A41P和1G相对罕见，频率分别仅为1.04%和0.52%。我们的研究结果提供了藏族个体中CYP3A4多态性的信息，这可能有助于通过为该民族提供个性化药物来优化药物治疗效果。
