Genetic Polymorphism of Cytochrome P450 (2C19) Enzyme in Iranian Turkman Ethnic Group

Overview

Journal Oman Med J

Specialty General Medicine

Date 2013 Aug 2

PMID 23904915

Citations 7

Authors

Robabeh Ghiyas Tabari

Abdoljalal Marjani

Ogholdondy Agh Ataby

Azad Reza Mansourian

Nader Mansour Samai

Affiliations

Soon will be listed here.

Abstract

Objective: Different findings indicate that CYP2C plays a clinical role in determining interindividual and interethnic differences in drug effectiveness. The ethnic differences in the frequency of CYP2C19 mutant alleles continue to be a significant study topic. The aim of the present study was to assess the frequency of allelic variants of CYP2C19 in Turkman ethnic groups and compare them with the frequencies in other ethnic populations.

Methods: The study group included 140 unrelated healthy ethnic Turkman subject referred to the Health Center. Genotyping of CYP2C19 alleles (CYP2C19*1, CYP2C19*2, and CYP2C19*3 alleles) was carried out by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism technique.

Results: The allele frequency of CYP2C19*1, CYP2C19*2 and CYP2C19*3 were 56.43%, 23.57% and 20%, respectively. The result also showed that 39.7% of subjects expressed the CYP2C19*1/*1 genotype. While 42.1%, 9.3%, 9.3% and 1.4% expressed CYP2C19*1/*2, CYP2C19*1/*3, CYP2C19*2/*2 and CYP2C19*3/*3 genotypes, respectively. The genotype CYP2C19*2/*3 was not expressed in this study population. The findings suggested that 10% of subjects were poor metabolizers by expressing CYP2C19*2/*2 and CYP2C19*3/*3 genotypes. Fifty one percent of subjects were intermediate metabolizers having CYP2C19*1/*2, CYP2C19*2/*3 and CYP2C19*1/*3 genotypes and 37.86% were found to be extensive metabolizers expressing CYP2C19*1/*1 genotype. The frequency of intermediate metabolizers genotype was high (51%) in Turkman ethnic groups.

Conclusion: This study showed that the determined allelic variants of CYP2C19 (CYP2C19*2 and CYP2C19*3 mutations) in Turkman ethnic group are comparable to other populations. These findings could be useful for the clinicians in different country to determine optimal dosage and effectiveness of drugs metabolized by this polymorphic enzyme.

Citing Articles

Importance of Pharmacogenetics and Drug-Drug Interactions in a Kidney Transplanted Patient.

Concha J, Sanguesa E, Saez-Benito A, Aznar I, Berenguer N, Saez-Benito L Life (Basel). 2023; 13(8).

PMID: 37629484 PMC: 10455535. DOI: 10.3390/life13081627.

Variations in the Frequencies of Polymorphisms in the CYP450s Genes in Eight Major Ethnicities of Iran: A Review of the Human Data.

Neyshaburinezhad N, Ghasim H, Rouini M, Daali Y, Ardakani Y J Pers Med. 2022; 12(11).

PMID: 36579562 PMC: 9697354. DOI: 10.3390/jpm12111848.

CYP2D6 and CYP2C19 Genes Associated with Tricontinental and Latin American Ancestry of Pe-ruvians.

Alvarado A, Saravia M, Losno R, Pariona R, Munoz A, Ybanez-Julca R Drug Metab Bioanal Lett. 2022; .

PMID: 36518034 PMC: 10436705. DOI: 10.2174/1872312815666221213151140.

Frequency of Important CYP450 Enzyme Gene Polymorphisms in the Iranian Population in Comparison with Other Major Populations: A Comprehensive Review of the Human Data.

Neyshaburinezhad N, Ghasim H, Rouini M, Daali Y, Ardakani Y J Pers Med. 2021; 11(8).

PMID: 34442448 PMC: 8401584. DOI: 10.3390/jpm11080804.

Genetic Polymorphism of CYP2C19 in Pakistani Population.

Riaz S, Muhammad Din S, Tareen M, Tariq F, Latif Y, Siddiqi S Iran J Pharm Res. 2019; 18(2):1097-1102.

PMID: 31531091 PMC: 6706708. DOI: 10.22037/ijpr.2019.1100644.

References

Dandara C, Masimirembwa C, Magimba A, Sayi J, Kaaya S, Sommers D . Genetic polymorphism of CYP2D6 and CYP2C19 in east- and southern African populations including psychiatric patients. Eur J Clin Pharmacol. 2001; 57(1):11-7. DOI: 10.1007/s002280100282. View

Sistonen J, Fuselli S, Palo J, Chauhan N, Padh H, Sajantila A . Pharmacogenetic variation at CYP2C9, CYP2C19, and CYP2D6 at global and microgeographic scales. Pharmacogenet Genomics. 2009; 19(2):170-9. DOI: 10.1097/FPC.0b013e32831ebb30. View

Chang M, Dahl M, Tybring G, Gotharson E, 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. 1995; 5(6):358-63. DOI: 10.1097/00008571-199512000-00004. View

Xie H, Kim R, Stein C, Wilkinson G, Wood A . Genetic polymorphism of (S)-mephenytoin 4'-hydroxylation in populations of African descent. Br J Clin Pharmacol. 1999; 48(3):402-8. PMC: 2014331. DOI: 10.1046/j.1365-2125.1999.00009.x. View

Hunfeld N, Mathot R, Touw D, van Schaik R, Mulder P, Franck P . Effect of CYP2C19*2 and *17 mutations on pharmacodynamics and kinetics of proton pump inhibitors in Caucasians. Br J Clin Pharmacol. 2008; 65(5):752-60. PMC: 2432487. DOI: 10.1111/j.1365-2125.2007.03094.x. View

Goldstein J, Blaisdell J . Genetic tests which identify the principal defects in CYP2C19 responsible for the polymorphism in mephenytoin metabolism. Methods Enzymol. 1996; 272:210-8. DOI: 10.1016/s0076-6879(96)72025-6. View

Shuldiner A, OConnell J, Bliden K, Gandhi A, Ryan K, Horenstein R . Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA. 2009; 302(8):849-57. PMC: 3641569. DOI: 10.1001/jama.2009.1232. View

Meyer U . Pharmacogenetics: the slow, the rapid, and the ultrarapid. Proc Natl Acad Sci U S A. 1994; 91(6):1983-4. PMC: 43291. DOI: 10.1073/pnas.91.6.1983. View

Nakamura K, Goto F, Ray W, McALLISTER C, Jacqz E, Wilkinson G . Interethnic differences in genetic polymorphism of debrisoquin and mephenytoin hydroxylation between Japanese and Caucasian populations. Clin Pharmacol Ther. 1985; 38(4):402-8. DOI: 10.1038/clpt.1985.194. View

10.

Bozina N, Granic P, Lalic Z, Tramisak I, Lovric M, Stavljenic-Rukavina A . Genetic polymorphisms of cytochromes P450: CYP2C9, CYP2C19, and CYP2D6 in Croatian population. Croat Med J. 2003; 44(4):425-8. View

11.

Masimirembwa C, Bertilsson L, Johansson I, Hasler J, Ingelman-Sundberg M . Phenotyping and genotyping of S-mephenytoin hydroxylase (cytochrome P450 2C19) in a Shona population of Zimbabwe. Clin Pharmacol Ther. 1995; 57(6):656-61. DOI: 10.1016/0009-9236(95)90228-7. View

12.

Allabi A, Gala J, Desager J, Heusterspreute M, Horsmans Y . Genetic polymorphisms of CYP2C9 and CYP2C19 in the Beninese and Belgian populations. Br J Clin Pharmacol. 2003; 56(6):653-7. PMC: 1884305. DOI: 10.1046/j.1365-2125.2003.01937.x. View

13.

Simon T, Verstuyft C, Mary-Krause M, Quteineh L, Drouet E, Meneveau N . Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med. 2008; 360(4):363-75. DOI: 10.1056/NEJMoa0808227. View

14.

Daly A . Pharmacogenetics of the major polymorphic metabolizing enzymes. Fundam Clin Pharmacol. 2003; 17(1):27-41. DOI: 10.1046/j.1472-8206.2003.00119.x. View

15.

Halling J, Petersen M, Damkier P, Nielsen F, Grandjean P, Weihe P . Polymorphism of CYP2D6, CYP2C19, CYP2C9 and CYP2C8 in the Faroese population. Eur J Clin Pharmacol. 2005; 61(7):491-7. DOI: 10.1007/s00228-005-0938-1. View

16.

de Morais S, Wilkinson G, Blaisdell J, Nakamura K, Meyer U, Goldstein J . The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans. J Biol Chem. 1994; 269(22):15419-22. View

17.

Pang Y, Yang Y, Wong L, Lee T, Mustafa A, Mohamed Z . Genetic polymorphism of cytochrome P450 2C19 in healthy Malaysian subjects. Br J Clin Pharmacol. 2004; 58(3):332-5. PMC: 1884559. DOI: 10.1111/j.1365-2125.2004.02144.x. View

18.

Scordo M, Caputi A, DArrigo C, Fava G, Spina E . Allele and genotype frequencies of CYP2C9, CYP2C19 and CYP2D6 in an Italian population. Pharmacol Res. 2004; 50(2):195-200. DOI: 10.1016/j.phrs.2004.01.004. View

19.

Gaikovitch E, Cascorbi I, Mrozikiewicz P, Brockmoller J, Frotschl R, Kopke K . Polymorphisms of drug-metabolizing enzymes CYP2C9, CYP2C19, CYP2D6, CYP1A1, NAT2 and of P-glycoprotein in a Russian population. Eur J Clin Pharmacol. 2003; 59(4):303-12. DOI: 10.1007/s00228-003-0606-2. View

20.

Takakubo F, Kuwano A, Kondo I . Evidence that poor metabolizers of (S)-mephenytoin could be identified by haplotypes of CYP2C19 in Japanese. Pharmacogenetics. 1996; 6(3):265-7. DOI: 10.1097/00008571-199606000-00011. View