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Genotype‑phenotype analysis of CYP2C19 in the Tibetan population and its potential clinical implications in drug therapy

  • Authors:
    • Tianbo Jin
    • Xiyang Zhang
    • Tingting Geng
    • Xugang Shi
    • Li Wang
    • Dongya Yuan
    • Longli Kang
  • View Affiliations / Copyright

    Affiliations: Key Laboratory of High Altitude Environment and Genes Related to Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi 712082, P.R. China, School of Life Sciences, Northwest University, Xi'an, Shaanxi 710069, P.R. China, Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710061, P.R. China
    Copyright: © Jin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2117-2123
    |
    Published online on: January 13, 2016
       https://doi.org/10.3892/mmr.2016.4776
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Abstract

Cytochrome P450 2C19 (CYP2C19) is a highly polymorphic gene, it codes for a protein responsible for the metabolism of multiple clinically important therapeutic agents. However, there is currently no available data on the distribution of CYP2C19 mutant alleles in the Tibetan population. The aim of the present study was to identify different CYP2C19 mutant alleles and determine their frequencies, along with genotypic frequencies, in the Tibetan population. The whole CYP2C19 gene was amplified and sequenced in 96 unrelated, healthy Tibetans from the Tibet Autonomous Region of China, the promoter region, exons, introns and the 3'‑UTR were screened for genetic variants. Three novel genetic polymorphisms in CYP2C19 were detected among a total of 27 different mutations. The allele frequencies of CYP2C19*1A, *1B, *2A, *3A and *17 were 50, 28.13, 15.10, 5.21 and 1.56%, respectively. The most common genotype combinations were CYP2C19*1A/*1B (56.25%) and *1A/*2A (30.21%). One novel non‑synonymous mutation (Asn to Lys) in CYP2C19 was identified, and this mutation was predicted to be intolerant and benign by SIFT and PolyPhen‑2, respectively. The observations of the present study may have important clinical implications for the use of medications metabolized by CYP2C19 among Tibetans.
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1 

Lee CR, Goldstein JA and Pieper JA: Cytochrome P450 2C9 polymorphisms: A comprehensive review of the in-vitro and human data. Pharmacogenetics. 12:251–263. 2002. View Article : Google Scholar : PubMed/NCBI

2 

Gerbal-Chaloin S, Pascussi JM, Pichard-Garcia L, Daujat M, Waechter F, Fabre JM, Carrère N and Maurel P: Induction of CYP2C genes in human hepatocytes in primary culture. Drug Metab Dispos. 29:242–251. 2001.PubMed/NCBI

3 

Andersson T, Holmberg J, Röhss K and Walan A: Pharmacokinetics and effect on caffeine metabolism of the proton pump inhibitors, omeprazole, lansoprazole and pantoprazole. Br J Clin Pharmacol. 45:369–375. 1998. View Article : Google Scholar : PubMed/NCBI

4 

Gardiner SJ and Begg EJ: Pharmacogenetics, drug-metabolizing enzymes, and clinical practice. Pharmacol Rev. 58:521–590. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Onof S, Hatanaka T, Miyazawa S, Tsutsui M, Aoyama T, Gonzalez FJ and Satoh T: Human liver microsomal diazepam metabolism using cDNA-expressed cytochrome P450s: Role of CYP2B6, 2C19 and the 3A subfamily. Xenobiotica. 26:1155–1166. 1996. View Article : Google Scholar

6 

Paveliu MS, Bengea S and Paveliu FS: Individualized drug response related to genetic variations of cytochrome P450 isoforms and other enzymes. Rev Farmacia. 58:245–254. 2010.

7 

Adrian A, Daniela C, Axente GI, Ionut O, Flavian R and Anamaria G: Detection of CYP2D6*6 allele by real time polymerase chain reaction in Romanian population. Rev Farmacia. 58:353–361. 2010.

8 

Goldstein JA: Clinical relevance of genetic polymorphisms in the human CYP2C subfamily. Br J Clin Pharmacol. 52:349–355. 2001. View Article : Google Scholar : PubMed/NCBI

9 

Chang M, Tybring G, Dahl ML and Lindh JD: Impact of cytochrome P450 2C19 polymorphisms on citalopram/escitalopram exposure: A systematic review and meta-analysis. Clin Pharmacokinet. 53:801–811. 2014. View Article : Google Scholar : PubMed/NCBI

10 

Serrano D, Torrado S, Torrado-Santiago S and Gisbert JP: The influence of CYP2C19 genetic polymorphism on the pharmacokinetics/-pharmacodynamics of proton pump inhibitor-containing Helicobacter pylori treatments. Curr Drug Metab. 13:1303–1312. 2012. View Article : Google Scholar : PubMed/NCBI

11 

Myrand SP, Sekiguchi K, Man MZ, Lin X, Tzeng RY, Teng CH, Hee B, Garrett M, Kikkawa H, Lin CY, et al: Pharmacokinetics/genotype associations for major cytochrome P450 enzymes in native and first-and third-generation Japanese populations: Comparison with Korean, Chinese and Caucasian populations. Clin Pharmacol Ther. 84:347–361. 2008. View Article : Google Scholar : PubMed/NCBI

12 

Adamec C: Example of the use of the nonparametric test. Test X2 for comparison of 2 independent examples. Cesk Zdrav. 12:613–619. 1964.In Czech. PubMed/NCBI

13 

Barrett JC, Fry B, Maller J and Daly MJ: Haploview: Analysis and visualization of LD and haplotype maps. Bioinformatics. 21:263–265. 2005. View Article : Google Scholar

14 

Ng PC and Henikoff S: Accounting for human polymorphisms predicted to affect protein function. Genome Res. 12:436–446. 2002. View Article : Google Scholar : PubMed/NCBI

15 

Meyer UA: Pharmacogenetics and adverse drug reactions. Lancet. 356:1667–1671. 2000. View Article : Google Scholar : PubMed/NCBI

16 

Zhou Q, Yu XM, Lin HB, Wang L, Yun QZ, Hu SN and Wang DM: Genetic polymorphism, linkage disequilibrium, haplotype structure and novel allele analysis of CYP2C19 and CYP2D6 in Han Chinese. Pharmacogenomics J. 9:380–394. 2009. View Article : Google Scholar : PubMed/NCBI

17 

He N, Yan FX, Huang SL, Wang W, Xiao ZS, Liu ZQ and Zhou HH: CYP2C19 genotype and S-mephenytoin 4′-hydroxylation phenotype in a Chinese Dai population. Eur J Clin Pharmacol. 58:15–18. 2002. View Article : Google Scholar : PubMed/NCBI

18 

Kimura M, Ieiri I, Mamiya K, Urae A and Higuchi S: Genetic polymorphism of cytochrome P450s, CYP2C19, and CYP2C9 in a Japanese population. Ther Drug Monit. 20:243–247. 1998. View Article : Google Scholar : PubMed/NCBI

19 

Roh HK, Dahl ML, Tybring G, Yamada H, Cha YN and Bertilsson L: CYP2C19 genotype and phenotype determined by omeprazole in a Korean population. Pharmacogenetics. 6:547–551. 1996. View Article : Google Scholar : PubMed/NCBI

20 

Yamada S, Onda M, Kato S, Matsuda N, Matsuhisa T, Yamada N, Miki M and Matsukura N: Genetic differences in CYP2C19 single nucleotide polymorphisms among four Asian populations. J Gastroenterol. 36:669–672. 2001. View Article : Google Scholar : PubMed/NCBI

21 

Chang M, Dahl ML, Tybring G, Götharson E and Bertilsson L: Use of omeprazole as a probe drug for CYP2C19 phenotype in Swedish Caucasians: Comparison with S-mephenytoin hydroxylation phenotype and CYP2C19 genotype. Pharmacogenetics. 5:358–363. 1995. View Article : Google Scholar : PubMed/NCBI

22 

Gaikovitch EA, Cascorbi I, Mrozikiewicz PM, Brockmöller J, Frötschl R, Köpke K, Gerloff T, Chernov JN and Roots I: Polymorphisms of drug-metabolizing enzymes CYP2C9, CYP2C19, CYP2D6, CYP1A1, NAT2 and of P-glycoprotein in a Russian population. Eur J Clin Pharmacol. 59:303–312. 2003. View Article : Google Scholar : PubMed/NCBI

23 

Scordo MG, Caputi AP, D'Arrigo C, Fava G and Spina E: Allele and genotype frequencies of CYP2C9, CYP2C19 and CYP2D6 in an Italian population. Pharmacol Res. 50:195–200. 2004. View Article : Google Scholar : PubMed/NCBI

24 

Bravo-Villalta HV, Yamamoto K, Nakamura K, Bayá A, Okada Y and Horiuchi R: Genetic polymorphism of CYP2C9 and CYP2C19 in a Bolivian population: An investigative and comparative study. Eur J Clin Pharmacol. 61:179–184. 2005. View Article : Google Scholar : PubMed/NCBI

25 

Halling J, Petersen MS, Damkier P, Nielsen F, Grandjean P, Weihe P, Lundgren S, Lundblad MS and Brøsen K: Polymorphism of CYP2D6, CYP2C19, CYP2C9 and CYP2C8 in the Faroese population. Eur J Clin Pharmacol. 61:491–497. 2005. View Article : Google Scholar : PubMed/NCBI

26 

Herrlin K, Massele AY, Jande M, Alm C, Tybring G, Abdi YA, Wennerholm A, Johansson I, Dahl ML, Bertilsson L and Gustafsson LL: Bantu tanzanians have a decreased capacity to metabolize omeprazole and mephenytoin in relation to their CYP2C19 genotype. Clin Pharmacol Ther. 64:391–401. 1998. View Article : Google Scholar : PubMed/NCBI

27 

Persson I, Aklillu E, Rodrigues F, Bertilsson L and Ingelman-Sundberg M: S-mephenytoin hydroxylation phenotype and CYP2C19 genotype among Ethiopians. Pharmacogenetics. 6:521–526. 1996. View Article : Google Scholar : PubMed/NCBI

28 

Masimirembwa C, Bertilsson L, Johansson I, Hasler JA and Ingelman-Sundberg M: Phenotyping and genotyping of S-mephenytoin hydroxylase (cytochrome P450 2C19) in a Shona population of Zimbabwe. Clin Pharmacol Ther. 57:656–661. 1995. View Article : Google Scholar : PubMed/NCBI

29 

Kóbori L, Kõhalmy K, Porrogi P, Sárváry E, Gerlei Z, Fazakas J, Nagy P, Járay J and Monostory K: Drug-induced liver graft toxicity caused by cytochrome P450 poor metabolism. Br J Clin Pharmacol. 65:428–436. 2008. View Article : Google Scholar

30 

Chen L, Qin S, Xie J, Tang J, Yang L, Shen W, Zhao X, Du J, He G, Feng G, et al: Genetic polymorphism analysis of CYP2C19 in Chinese Han populations from different geographic areas of mainland China. Pharmacogenomics. 9:691–702. 2008. View Article : Google Scholar : PubMed/NCBI

31 

Desta Z, Zhao X, Shin JG and Flockhart DA: Clinical significance of the cytochrome P450 2C19 genetic polymorphism. Clin Pharmacokinet. 41:913–958. 2002. View Article : Google Scholar : PubMed/NCBI

32 

Anichavezhi D, Chakradhara Rao US, Shewade DG, Krishnamoorthy R and Adithan C: Distribution of CYP2C19*17 allele and genotypes in an Indian population. J Clin Pharm Ther. 37:313–318. 2012. View Article : Google Scholar

33 

Gurbel PA, Shuldiner AR, Bliden KP, Ryan K, Pakyz RE and Tantry US: The relation between CYP2C19 genotype and phenotype in stented patients on maintenance dual antiplatelet therapy. Am Heart J. 161:598–604. 2011. View Article : Google Scholar : PubMed/NCBI

34 

Mega JL, Simon T, Collet JP, Anderson JL, Antman EM, Bliden K, Cannon CP, Danchin N, Giusti B, Gurbel P, Horne BD, Hulot JS, Kastrati A, Montalescot G, Neumann FJ, Shen L, Sibbing D, Steg PG, Trenk D, Wiviott SD and Sabatine MS: Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. JAMA. 304:1821–1830. 2010. View Article : Google Scholar : PubMed/NCBI

35 

Collet JP, Hulot JS, Pena A, Villard E, Esteve JB, Silvain J, Payot L, Brugier D, Cayla G, Beygui F, et al: Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: A cohort study. Lancet. 373:309–317. 2009. View Article : Google Scholar

36 

Ng PC and Henikoff S: Predicting the effects of amino acid substitutions on protein function. Annu Rev Genomics Hum Genet. 7:61–80. 2006. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Jin T, Zhang X, Geng T, Shi X, Wang L, Yuan D and Kang L: Genotype‑phenotype analysis of CYP2C19 in the Tibetan population and its potential clinical implications in drug therapy. Mol Med Rep 13: 2117-2123, 2016.
APA
Jin, T., Zhang, X., Geng, T., Shi, X., Wang, L., Yuan, D., & Kang, L. (2016). Genotype‑phenotype analysis of CYP2C19 in the Tibetan population and its potential clinical implications in drug therapy. Molecular Medicine Reports, 13, 2117-2123. https://doi.org/10.3892/mmr.2016.4776
MLA
Jin, T., Zhang, X., Geng, T., Shi, X., Wang, L., Yuan, D., Kang, L."Genotype‑phenotype analysis of CYP2C19 in the Tibetan population and its potential clinical implications in drug therapy". Molecular Medicine Reports 13.3 (2016): 2117-2123.
Chicago
Jin, T., Zhang, X., Geng, T., Shi, X., Wang, L., Yuan, D., Kang, L."Genotype‑phenotype analysis of CYP2C19 in the Tibetan population and its potential clinical implications in drug therapy". Molecular Medicine Reports 13, no. 3 (2016): 2117-2123. https://doi.org/10.3892/mmr.2016.4776
Copy and paste a formatted citation
x
Spandidos Publications style
Jin T, Zhang X, Geng T, Shi X, Wang L, Yuan D and Kang L: Genotype‑phenotype analysis of CYP2C19 in the Tibetan population and its potential clinical implications in drug therapy. Mol Med Rep 13: 2117-2123, 2016.
APA
Jin, T., Zhang, X., Geng, T., Shi, X., Wang, L., Yuan, D., & Kang, L. (2016). Genotype‑phenotype analysis of CYP2C19 in the Tibetan population and its potential clinical implications in drug therapy. Molecular Medicine Reports, 13, 2117-2123. https://doi.org/10.3892/mmr.2016.4776
MLA
Jin, T., Zhang, X., Geng, T., Shi, X., Wang, L., Yuan, D., Kang, L."Genotype‑phenotype analysis of CYP2C19 in the Tibetan population and its potential clinical implications in drug therapy". Molecular Medicine Reports 13.3 (2016): 2117-2123.
Chicago
Jin, T., Zhang, X., Geng, T., Shi, X., Wang, L., Yuan, D., Kang, L."Genotype‑phenotype analysis of CYP2C19 in the Tibetan population and its potential clinical implications in drug therapy". Molecular Medicine Reports 13, no. 3 (2016): 2117-2123. https://doi.org/10.3892/mmr.2016.4776
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