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Original article
Genetic architectures of ADME genes in five Eurasian admixed populations and implications for drug safety and efficacy
  1. Jing Li1,
  2. Haiyi Lou1,
  3. Xiong Yang1,
  4. Dongsheng Lu1,
  5. Shilin Li2,
  6. Li Jin2,
  7. Xinwei Pan2,
  8. Wenjun Yang3,
  9. Manshu Song4,
  10. Dolikun Mamatyusupu5,
  11. Shuhua Xu1
  1. 1Max Planck Independent Research Group on Population Genomics, Chinese Academy of Sciences and Max Planck Society (CAS-MPG) Partner Institute for Computational Biology (PICB), Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
  2. 2State Key Laboratory of Genetic Engineering and Ministry of Education (MOE) Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China
  3. 3Key Laboratory of Reproduction and Heredity of Ningxia Region, Ningxia Medical University, Yinchuan, Ningxia, China
  4. 4School of Public Health, Capital Medical University and Municipal Key Laboratory of Clinical Epidemiology, Beijing, China
  5. 5College of the Life Sciences and Technology, Xinjiang University, Urumqi, China
  1. Correspondence to Professor Shuhua Xu, Max Planck Independent Research Group on Population Genomics, Chinese Academy of Sciences and Max Planck Society (CAS-MPG) Partner Institute for Computational Biology (PICB), Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; xushua{at}picb.ac.cn

Abstract

Background Drug absorption, distribution, metabolism and excretion (ADME) contribute to the high heterogeneity of drug responses in humans. However, the same standard for drug dosage has been applied to all populations in China although genetic differences in ADME genes are expected to exist in different ethnic groups. In particular, the ethnic minorities in northwestern China with substantial ancestry contribution from Western Eurasian people might violate such a single unified standard.

Methods In this study, we used Affymetrix SNP Array 6.0 to investigate the genetic diversity of 282 ADME genes in five northwestern Chinese minority populations, namely, Tajik, Uyghur, Kazakh, Kirgiz and Hui, and attempted to identify the highly differential SNPs and haplotypes and further explore their clinical implications.

Results We found that genetic diversity of many ADME genes in the five minority groups was substantially different from those in the Han Chinese population. For instance, we identified 10 functional SNPs with substantial allele frequency differences, 14 functional SNPs with highly different heterozygous states and eight genes with significant haplotype differences between these admixed minority populations and the Han Chinese population. We further confirmed that these differences mainly resulted from the European gene flow, that is, this gene flow increased the genetic diversity in the admixed populations.

Conclusions These results suggest that the ADME genes vary substantially among different Chinese ethnic groups. We suggest it could cause potential clinical risk if the same dosage of substances (eg, antitumour drugs) is used without considering population stratification.

  • Molecular genetics
  • Microarray
  • Genome-wide

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