The population genetics of pharmacogenomics VIP variants in the Sherpa population.

Drug Metab Pharmacokinet

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 Molecular Genetic Mechanisms and Intervention Research on High Altitude Disease of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi 712082, China; School of Life Sciences, Northwest University, Xi'an, Shaanxi 710069, China; National Engineering Research Center for Miniaturized Detection Systems, Xi'an, Shaanxi 710069, China. Electronic address:

Published: February 2016

Polymorphic distributions of pharmacogenes among some ethnicities are under-represented in current pharmacogenetic research. Particularly, there is a paucity of pharmacogenetic information in the Sherpa population in Tibet. We used the Sequenom MassARRAY single nucleotide polymorphism (SNP) genotyping technology to detect 86 very important pharmacogene (VIP) variants in Sherpas and compared the genotypic frequencies of these variants with HapMap populations. Overall, 59 of the 60 previously reported variants in the HapMap populations were found in our study. We found minimal differences between populations of Sherpas and Chinese Han in Beijing (CHB), Chinese in Metropolitan Denver, Colorado (CHD), Japanese in Tokyo, Japan (JPT), and Mexicans in Los Angeles, California (MEX) after a strict Bonferroni correction. Only 8, 4, 5, 4 VIP genotypes, respectively, were different in these groups. Additionally, pairwise FST values and clustering analyses showed that the VIP variants in the Sherpa population exhibited a close genetic affinity with the CHB and JPT populations, but they were most similar to the CHD population. Our results contribute to a better understanding of the molecular basis underlying ethnic differences in drug response, which may potentially benefit the development of personalized medicine for the Sherpa population.

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Source
http://dx.doi.org/10.1016/j.dmpk.2015.11.007DOI Listing

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