Mengdan Yan1, Dianzhen Li1, Guige Zhao1, Jing Li1, Fanglin Niu1, Bin Li1, Peng Chen1, Tianbo Jin2. 1. 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. 2. 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. Electronic address: jintianbo@gmail.com.
Abstract
INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.