期刊论文详细信息
BMC Genetics
Genetic polymorphisms of pharmacogenomic VIP variants in the Uygur population from northwestern China
Jie Yang1  Tianbo Jin2  Yuan Zhang2  Bo Wang2  Tingting Geng2  Shuli Du2  Ayiguli Yibulayin1  Ainiwaer Aikemu3  Li Wang4 
[1] Department of radiotherapy two, The people’s hospital of Xinjiang Uygur Autonomous Region, #91 Tianchi Road, Urumqi 830001, , Xinjiang, China;National Engineering Research Center for Miniaturized Detection Systems, Xi’an 710069, China;Department of Drug Analysis, Faculty of Pharmacy, Xinjiang Medical University, Urumqi 830054, China;Key Laboratory of High Altitude Environment and Genes Related to Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang 712082, Shaanxi, China
关键词: VIP variants;    Uygur;    genetic polymorphisms;    Pharmacogenomics;   
Others  :  1216012
DOI  :  10.1186/s12863-015-0232-x
 received in 2015-01-17, accepted in 2015-06-16,  发布年份 2015
PDF
【 摘 要 】

Background

Drug response variability observed amongst patients is caused by the interaction of both genetic and non-genetic factors, and frequencies of functional genetic variants are known to vary amongst populations. Pharmacogenomic research has the potential to help with individualized treatments. We have not found any pharmacogenomics information regarding Uygur ethnic group in northwest China. In the present study, we genotyped 85 very important pharmacogenetic (VIP) variants (selected from the PharmGKB database) in the Uygur population and compared our data with other eleven populations from the HapMap data set.

Results

Through statistical analysis, we found that CYP3A5 rs776746, VKORC1 rs9934438, and VKORC1 rs7294 were most different in Uygur compared with most of the eleven populations from the HapMap data set. Compared with East Asia populations, allele A of rs776746 is less frequent and allele A of rs7294 is more frequent in the Uygur population. The analysis of F-statistics (Fst) and population structure shows that the genetic background of Uygur is relatively close to that of MEX.

Conclusions

Our results show significant differences amongst Chinese populations that will help clinicians triage patients for better individualized treatments.

【 授权许可】

   
2015 Wang et al.

【 预 览 】
附件列表
Files Size Format View
20150628010554963.pdf 874KB PDF download
Fig. 1. 107KB Image download
【 图 表 】

Fig. 1.

【 参考文献 】
  • [1]Evans WE, Johnson JA. Pharmacogenomics: the inherited basis for interindividual differences in drug response. Annu Rev Genomics Hum Genet. 2001; 2:9-39.
  • [2]Szekanecz Z, Mesko B, Poliska S, Vancsa A, Szamosi S, Vegh E, Simkovics E, Laki J, Kurko J, Besenyei T et al.. Pharmacogenetics and pharmacogenomics in rheumatology. Immunol Res. 2013; 56(2–3):325-333.
  • [3]Evans WE, McLeod HL. Pharmacogenomics–drug disposition, drug targets, and side effects. N Engl J Med. 2003; 348(6):538-549.
  • [4]Peet NP, Bey P. Pharmacogenomics: challenges and opportunities. Drug Discov Today. 2001; 6(10):495-498.
  • [5]Peters EJ, McLeod HL. Ability of whole-genome SNP arrays to capture ‘must have’ pharmacogenomic variants. Pharmacogenomics. 2008; 9(11):1573-1577.
  • [6]Gabriel S, Ziaugra L, Tabbaa D. SNP genotyping using the Sequenom MassARRAY iPLEX platform. Curr Protoc Hum Genet. 2009:2.12. 11–12.12. 16. doi:10.1002/0471142905.hg0212s60
  • [7]Thomas RK, Baker AC, Debiasi RM, Winckler W, Laframboise T, Lin WM, Wang M, Feng W, Zander T, MacConaill L et al.. High-throughput oncogene mutation profiling in human cancer. Nat Genet. 2007; 39(3):347-351.
  • [8]Elhaik E. Empirical distributions of FST from large-scale human polymorphism data. PLoS One. 2012; 7(11): Article ID e49837
  • [9]Holsinger KE, Weir BS. Genetics in geographically structured populations: defining, estimating and interpreting FST. Nat Rev Genet. 2009; 10(9):639-650.
  • [10]Excoffier L, Laval G, Schneider S. Arlequin (version 3.0): an integrated software package for population genetics data analysis. Evol Bioinformatics Online. 2005; 1:47.
  • [11]Reynolds J, Weir B, Cockerham CC. Estimation of the coancestry coefficient: basis for a short-term genetic distance. Genetics. 1983; 105(3):767-779.
  • [12]Pritchard JK, Stephens M, Donnelly P. Inference of population structure using multilocus genotype data. Genetics. 2000; 155(2):945-959.
  • [13]Evanno G, Regnaut S, Goudet J. Detecting the number of clusters of individuals using the software STRUCTURE: a simulation study. Mol Ecol. 2005; 14(8):2611-2620.
  • [14]Suarez-Kurtz G, Vargens DD, Santoro AB, Hutz MH, de Moraes ME, Pena SD, Ribeiro-dos-Santos Â, Romano-Silva MA, Struchiner CJ. Global Pharmacogenomics: Distribution of CYP3A5 Polymorphisms and Phenotypes in the Brazilian Population. PLoS One. 2014; 9(1): Article ID e83472
  • [15]Lamba J, Hebert JM, Schuetz EG, Klein TE, Altman RB. PharmGKB summary: very important pharmacogene information for CYP3A5. Pharmacogenet Genomics. 2012; 22(7):555.
  • [16]Passey C, Birnbaum AK, Brundage RC, Oetting WS, Israni AK, Jacobson PA. Dosing equation for tacrolimus using genetic variants and clinical factors. Br J Clin Pharmacol. 2011; 72(6):948-957.
  • [17]Borobia AM, Romero I, Jimenez C, Gil F, Ramirez E, De Gracia R, Escuin F, Gonzalez E, Sansuán AJC. Trough tacrolimus concentrations in the first week after kidney transplantation are related to acute rejection. Ther Drug Monit. 2009; 31(4):436-442.
  • [18]O’Seaghdha C, McQuillan R, Moran A, Lavin P, Dorman A, O’Kelly P, Mohan D, Little P, Hickey D, Conlon P. Higher tacrolimus trough levels on days 2–5 post‐renal transplant are associated with reduced rates of acute rejection. Clin Transpl. 2009; 23(4):462-468.
  • [19]Laskow DA, Vincenti F, Neylan JF, Mendez R, Matas AJ. AN OPEN-LABEL, CONCENTRATION-RANGING TRIAL OF FK506 IN PRIMARY KIDNEY TRANSPLANTATION: A Report Of The United States Multicenter FK506 Kidney Transplant Group1. Transplantation. 1996; 62(7):900-905.
  • [20]Seo T, Nakada N, Ueda N, Hagiwara T, Hashimoto N, Nakagawa K, Ishitsu T. Effect of CYP3A5*3 on carbamazepine pharmacokinetics in Japanese patients with epilepsy. Clin Pharmacol Ther. 2006; 79(5):509-510.
  • [21]Park PW, Seo Y, Ahn J, Kim KA, Park JY. Effect of CYP3A5* 3 genotype on serum carbamazepine concentrations at steady‐state in Korean epileptic patients. J Clin Pharm Ther. 2009; 34(5):569-574.
  • [22]Zhu X, Yun W, Sun X, Qiu F, Zhao L, Guo Y. Effects of major transporter and metabolizing enzyme gene polymorphisms on carbamazepine metabolism in Chinese patients with epilepsy. Pharmacogenomics. 2014; 15(15):1867-1879.
  • [23]Rost S, Fregin A, Ivaskevicius V, Conzelmann E, Hortnagel K, Pelz HJ, Lappegard K, Seifried E, Scharrer I, Tuddenham EG et al.. Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature. 2004; 427(6974):537-541.
  • [24]D'Andrea G, D'Ambrosio RL, Di Perna P, Chetta M, Santacroce R, Brancaccio V, Grandone E, Margaglione M. A polymorphism in the VKORC1 gene is associated with an interindividual variability in the dose-anticoagulant effect of warfarin. Blood. 2005; 105(2):645-649.
  • [25]Reitsma PH, Van Der Heijden JF, Groot AP, Rosendaal FR, Büller HR. A C1173T dimorphism in the VKORC1 gene determines coumarin sensitivity and bleeding risk. PLoS Med. 2005; 2(10): Article ID e312
  • [26]Markatos CN, Grouzi E, Politou M, Gialeraki A, Merkouri E, Panagou I, Spiliotopoulou I, Travlou A. VKORC1 and CYP2C9 allelic variants influence acenocoumarol dose requirements in Greek patients. Pharmacogenomics. 2008; 9(11):1631-1638.
  • [27]Cadamuro J, Dieplinger B, Felder T, Kedenko I, Mueller T, Haltmayer M, Patsch W, Oberkofler H. Genetic determinants of acenocoumarol and phenprocoumon maintenance dose requirements. Eur J Clin Pharmacol. 2010; 66(3):253-260.
  • [28]Kovac MK, Maslac AR, Rakicevic LB, Radojkovic DP. The c.-1639G> A polymorphism of the VKORC1 gene in Serbian population: retrospective study of the variability in response to oral anticoagulant therapy. Blood Coagul Fibrinolysis. 2010; 21(6):558-563.
  • [29]Esmerian MO, Mitri Z, Habbal MZ, Geryess E, Zaatari G, Alam S, Skouri HN, Mahfouz RA, Taher A, Zgheib NK. Influence of CYP2C9 and VKORC1 polymorphisms on warfarin and acenocoumarol in a sample of Lebanese people. J Clin Pharmacol. 2011; 51(10):1418-1428.
  • [30]Rettie AE, Tai G. The pharmocogenomics of warfarin: closing in on personalized medicine. Mol Interv. 2006; 6(4):223-227.
  • [31]Limdi NA, Wadelius M, Cavallari L, Eriksson N, Crawford DC, Lee MT, Chen CH, Motsinger-Reif A, Sagreiya H, Liu N et al.. Warfarin pharmacogenetics: a single VKORC1 polymorphism is predictive of dose across 3 racial groups. Blood. 2010; 115(18):3827-3834.
  • [32]Wadelius M, Chen LY, Downes K, Ghori J, Hunt S, Eriksson N, Wallerman O, Melhus H, Wadelius C, Bentley D et al.. Common VKORC1 and GGCX polymorphisms associated with warfarin dose. Pharmacogenomics J. 2005; 5(4):262-270.
  • [33]Herman D, Peternel P, Stegnar M, Breskvar K, Dolzan V. The influence of sequence variations in factor VII, gamma-glutamyl carboxylase and vitamin K epoxide reductase complex genes on warfarin dose requirement. Thromb Haemostasis-Stuttg. 2006; 95(5):782.
  文献评价指标  
  下载次数:30次 浏览次数:19次