Yongjun He1, Hua Yang2, Tingting Geng3, Tian Feng3, Dongya Yuan1, Longli Kang1, Manling Luo4, Tianbo Jin5. 1. Key Laboratory for Basic Life Science Research 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. 2. School of Life Sciences, Northwest University Xi'an, Shaanxi 710069, China ; National Engineering Research Center for Miniaturized Detection Systems Xi'an, Shaanxi 710069, China. 3. National Engineering Research Center for Miniaturized Detection Systems Xi'an, Shaanxi 710069, China. 4. Department of Blood Transfusion, Second People's Hospital Kunming 650021, Yunnan Province, China. 5. Key Laboratory for Basic Life Science Research 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.
Abstract
BACKGROUND: It is well-established that differences among ethnic groups in drug responses are primarily due to the genetic diversity of pharmacogenes. A number of genes or variants that play a crucial role in drug responses have been designated Very Important Pharmacogenes (VIP) by the PharmGKB database. Clarifying the polymorphic distribution of VIPs in different ethnic groups will aid in personalized medicine for specific populations. METHODS: We sequenced 85 VIP variants in the Lhoba population based on the PharmGKB database. The polymorphic distribution of the 85 VIP variants in 100 Lhoba subjects was determined and compared with that of 11 major HapMap populations, including ASW, CEU, CHB, CHD, GIH, JPT, LWK, MEX, MKK, TSI, and YRI. We used χ(2) tests to identify significantly different loci between these populations. We downloaded SNP allele frequencies from the ALlele FREquency Database to observe the global genetic variation distribution for these specific loci. And then we used Structure software to perform the genetic structure analysis of 12 populations. RESULTS: Based on comparisons of selected available loci, we found that 23, 28, 16, 10, 20, 16, 24, 19, 22, 21 and 36 of the selected VIP variant genotype frequencies in the Lhoba population differed from those of the ASW, CEU, CHB, CHD, GIH, JPT, LWK, MEX, MKK, TSI, and YRI populations, respectively. In addition, Pairwise FST values and clustering analyses also showed the VIP variants in Lhoba exhibited a close genetic affinity with CHD, CHB and JPT populations. CONCLUSION: Our results complement pharmacogenomic data on the Lhoba ethnic group and may be helpful in the diagnosis of certain diseases in minorities.
BACKGROUND: It is well-established that differences among ethnic groups in drug responses are primarily due to the genetic diversity of pharmacogenes. A number of genes or variants that play a crucial role in drug responses have been designated Very Important Pharmacogenes (VIP) by the PharmGKB database. Clarifying the polymorphic distribution of VIPs in different ethnic groups will aid in personalized medicine for specific populations. METHODS: We sequenced 85 VIP variants in the Lhoba population based on the PharmGKB database. The polymorphic distribution of the 85 VIP variants in 100 Lhoba subjects was determined and compared with that of 11 major HapMap populations, including ASW, CEU, CHB, CHD, GIH, JPT, LWK, MEX, MKK, TSI, and YRI. We used χ(2) tests to identify significantly different loci between these populations. We downloaded SNP allele frequencies from the ALlele FREquency Database to observe the global genetic variation distribution for these specific loci. And then we used Structure software to perform the genetic structure analysis of 12 populations. RESULTS: Based on comparisons of selected available loci, we found that 23, 28, 16, 10, 20, 16, 24, 19, 22, 21 and 36 of the selected VIP variant genotype frequencies in the Lhoba population differed from those of the ASW, CEU, CHB, CHD, GIH, JPT, LWK, MEX, MKK, TSI, and YRI populations, respectively. In addition, Pairwise FST values and clustering analyses also showed the VIP variants in Lhoba exhibited a close genetic affinity with CHD, CHB and JPT populations. CONCLUSION: Our results complement pharmacogenomic data on the Lhoba ethnic group and may be helpful in the diagnosis of certain diseases in minorities.
Authors: S Gerbal-Chaloin; J M Pascussi; L Pichard-Garcia; M Daujat; F Waechter; J M Fabre; N Carrère; P Maurel Journal: Drug Metab Dispos Date: 2001-03 Impact factor: 3.922
Authors: Veryan Codd; Massimo Mangino; Pim van der Harst; Peter S Braund; Michael Kaiser; Alan J Beveridge; Suzanne Rafelt; Jasbir Moore; Chris Nelson; Nicole Soranzo; Guangju Zhai; Ana M Valdes; Hannah Blackburn; Irene Mateo Leach; Rudolf A de Boer; Masayuki Kimura; Abraham Aviv; Alison H Goodall; Willem Ouwehand; Dirk J van Veldhuisen; Wiek H van Gilst; Gerjan Navis; Paul R Burton; Martin D Tobin; Alistair S Hall; John R Thompson; Tim Spector; Nilesh J Samani Journal: Nat Genet Date: 2010-02-07 Impact factor: 38.330