Yan Mengdan, Li Dianzhen, Zhao Guige, Li Jing, Niu Fanglin, Li Bin, Chen Peng, Jin Tianbo
Key Laboratory of Resource Biology and Biotechnology in Western China, Northwest University, Ministry of Education, Xi'an, Shaanxi 710069, China; College of Life Science, Northwest University, Xi'an, Shaanxi 710069, China.
Key Laboratory of Resource Biology and Biotechnology in Western China, Northwest University, Ministry of Education, Xi'an, Shaanxi 710069, China; College of Life Science, Northwest University, Xi'an, Shaanxi 710069, China; Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi 712082, China; Key Laboratory of High Altitude Environment and Genes Related to Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi 712082, China; Key Laboratory for Basic Life Science Research of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi 712082, China.
Gene. 2018 Mar 30;648:54-62. doi: 10.1016/j.gene.2018.01.040. Epub 2018 Jan 12.
Drug response and target therapeutic dosage are different among individuals. The variability is largely genetically determined. With the development of pharmacogenetics and pharmacogenomics, widespread research have provided us a wealth of information on drug-related genetic polymorphisms, and the very important pharmacogenetic (VIP) variants have been identified for the major populations around the world whereas less is known regarding minorities in China, including the Yi ethnic group. Our research aims to screen the potential genetic variants in Yi population on pharmacogenomics and provide a theoretical basis for future medication guidance.
In the present study, 80 VIP variants (selected from the PharmGKB database) were genotyped in 100 unrelated and healthy Yi adults recruited for our research. Through statistical analysis, we made a comparison between the Yi and other 11 populations listed in the HapMap database for significant SNPs detection. Two specific SNPs were subsequently enrolled in an observation on global allele distribution with the frequencies downloaded from ALlele FREquency Database. Moreover, F-statistics (Fst), genetic structure and phylogenetic tree analyses were conducted for determination of genetic similarity between the 12 ethnic groups.
Using the χ2 tests, rs1128503 (ABCB1), rs7294 (VKORC1), rs9934438 (VKORC1), rs1540339 (VDR) and rs689466 (PTGS2) were identified as the significantly different loci for further analysis. The global allele distribution revealed that the allele "A" of rs1540339 and rs9934438 were more frequent in Yi people, which was consistent with the most populations in East Asia. F-statistics (Fst), genetic structure and phylogenetic tree analyses demonstrated that the Yi and CHD shared a closest relationship on their genetic backgrounds. Additionally, Yi was considered similar to the Han people from Shaanxi province among the domestic ethnic populations in China.
Our results demonstrated significant differences on several polymorphic SNPs and supplement the pharmacogenomic information for the Yi population, which could provide new strategies for optimizing clinical medication in accordance with the genetic determinants of drug toxicity and efficacy.
个体之间的药物反应和目标治疗剂量存在差异。这种变异性在很大程度上由基因决定。随着药物遗传学和药物基因组学的发展，广泛的研究为我们提供了大量关于药物相关基因多态性的信息，并且已经为世界主要人群确定了非常重要的药物遗传学（VIP）变异，而关于中国少数民族，包括彝族的了解较少。我们的研究旨在筛选彝族人群药物基因组学中的潜在基因变异，并为未来的用药指导提供理论依据。
在本研究中，对为我们的研究招募的100名无亲缘关系的健康彝族成年人进行了80个VIP变异（从PharmGKB数据库中选择）的基因分型。通过统计分析，我们将彝族与HapMap数据库中列出的其他11个人群进行比较，以检测显著的单核苷酸多态性（SNP）。随后，从等位基因频率数据库下载频率，将两个特定的SNP纳入全球等位基因分布观察。此外，进行了F统计量（Fst）、遗传结构和系统发育树分析，以确定12个民族之间的遗传相似性。
使用χ2检验，rs1128503（ABCB1）、rs7294（VKORC1）、rs9934438（VKORC1）、rs1540339（VDR）和rs689466（PTGS2）被确定为有显著差异的位点，用于进一步分析。全球等位基因分布显示，rs1540339和rs9934438的等位基因“A”在彝族人群中更为常见，这与东亚的大多数人群一致。F统计量（Fst）、遗传结构和系统发育树分析表明，彝族和汉族在遗传背景上关系最为密切。此外，在中国国内民族中，彝族被认为与陕西省的汉族相似。
我们的结果表明，在几个多态性SNP上存在显著差异，并补充了彝族人群的药物基因组学信息，这可以根据药物毒性和疗效的遗传决定因素为优化临床用药提供新策略。
