Wang Li, Ren Yongchao, Shi Xugang, Yuan Dongya, Liu Kai, Geng Tingting, Li Gang, Kang Longli, Jin Tian-Bo
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.
Drug Metab Pharmacokinet. 2016 Feb;31(1):82-89. doi: 10.1016/j.dmpk.2015.11.007. Epub 2015 Dec 11.
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.
目前的药物遗传学研究中,某些种族中药物基因的多态性分布未得到充分体现。特别是,西藏夏尔巴人群中的药物遗传学信息匮乏。我们使用Sequenom MassARRAY单核苷酸多态性(SNP)基因分型技术检测了夏尔巴人中86个非常重要的药物基因(VIP)变异,并将这些变异的基因型频率与HapMap人群进行了比较。总体而言,我们的研究中发现了HapMap人群中先前报道的60个变异中的59个。经过严格的Bonferroni校正后,我们发现夏尔巴人群与北京汉族(CHB)、科罗拉多州丹佛市的中国人(CHD)、日本东京的日本人(JPT)和加利福尼亚州洛杉矶的墨西哥人(MEX)之间的差异极小。在这些组中,分别只有8个、4个、5个、4个VIP基因型存在差异。此外,成对FST值和聚类分析表明,夏尔巴人群中的VIP变异与CHB和JPT人群表现出密切的遗传亲和力,但它们与CHD人群最为相似。我们的研究结果有助于更好地理解药物反应种族差异背后的分子基础,这可能会为夏尔巴人群的个性化医疗发展带来潜在益处。