Prevalence of the CYP2C19*2 (681 G>A), *3 (636 G>A) and *17 (‑806 C>T) alleles among an Iranian population of different ethnicities

Dehbozorgi,Mahshid; Kamalidehghan,Behnam; Hosseini,Iman; Dehghanfard,Zahra; Sangtarash,Mohammad   Hossein; Firoozi,Maryam; Ahmadipour,Fatemeh; Meng,Goh  Yong; Houshmand,Massoud

doi:10.3892/mmr.2018.8377

Prevalence of the CYP2C192 (681 G>A), 3 (636 G>A) and *17 (‑806 C>T) alleles among an Iranian population of different ethnicities

Authors:
- Mahshid Dehbozorgi
- Behnam Kamalidehghan
- Iman Hosseini
- Zahra Dehghanfard
- Mohammad Hossein Sangtarash
- Maryam Firoozi
- Fatemeh Ahmadipour
- Goh Yong Meng
- Massoud Houshmand
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Affiliations: Department of Biology, University of Sistan and Baluchestan, Zahedan 98155‑987, Iran, Medical Genetics Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 198396‑3113, Iran, Department of Cellular and Molecular Biology, Nourdanesh Institute of Higher Education, Isfahan 8351711111, Iran, Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology, Tehran 14965/161, Iran, Pharmacy Department, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia, Department of Preclinical Sciences, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Selangor 43400, Malaysia
Published online on: January 5, 2018 https://doi.org/10.3892/mmr.2018.8377
Pages: 4195-4202
Copyright: © Dehbozorgi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Polymorphisms in the cytochrome P (CYP) 450 family may cause adverse drug responses in individuals. Cytochrome P450 2C19 (CYP2C19) is a member of the CYP family, where the presence of the 681 G>A, 636 G>A and 806 C>T polymorphisms result in the CYP2C19*2, CYP2C19*3 and CYP2C19*17 alleles, respectively. In the current study, the frequency of the CYP2C19*2, CYP2C19*3 and CYP2C19*17 alleles in an Iranian population cohort of different ethnicities were examined and then compared with previously published frequencies within other populations. Allelic and genotypic frequencies of the CYP2C19 alleles (*2, *3 and *17) were detected using polymerase chain reaction (PCR)‑restriction fragment length polymorphism analysis, PCR‑single‑strand conformation polymorphism analysis and DNA sequencing from blood samples of 1,229 unrelated healthy individuals from different ethnicities within the Iranian population. The CYP2C19 allele frequencies among the Iranian population were 21.4, 1.7, and 27.1% for the CYP2C19*2, CYP2C19*3 and CYP2C19*17 alleles, respectively. The frequency of the homozygous A/A variant of the CYP2C19*2 allele was significantly high and low in the Lur (P<0.001) and Caspian (P<0.001) ethnicities, respectively. However, the frequency of the homozygous A/A variant of the CYP2C19*3 allele was not detected in the Iranian cohort in the current study. The frequency of the heterozygous G/A variant of the CYP2C19*3 allele had the significantly highest and lowest frequency in the Fars (P<0.001) and Lur (P<0.001) groups, respectively. The allele frequency of the homozygous T/T variant of the CYP2C19*17 allele was significantly high in the Caspian (P<0.001) and low in the Kurd (P<0.05) groups. The frequency of the CYP2C19 alleles involved in drug metabolism, may improve the clinical understanding of the ethnic differences in drug responses, resulting in the advancement of the personalized medicine among the different ethnicities within the Iranian population.

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1	Hamdy SI, Hiratsuka M, Narahara K, El-Enany M, Moursi N, Ahmed MS and Mizugaki M: Allele and genotype frequencies of polymorphic cytochromes P450 (CYP2C9, CYP2C19, CYP2E1) and dihydropyrimidine dehydrogenase (DPYD) in the Egyptian population. Br J Clin Pharmacol. 53:596–603. 2002. View Article : Google Scholar : PubMed/NCBI
2	Wang H, An N, Wang H, Gao Y, Liu D, Bian T, Zhu J and Chen C: Evaluation of the effects of 20 nonsynonymous single nucleotide polymorphisms of CYP2C19 on S-mephenytoin 4′-hydroxylation and omeprazole 5′-hydroxylation. Drug Metab Dispos. 39:830–837. 2011. View Article : Google Scholar : PubMed/NCBI
3	Chaudhry A, Kochhar R and Kohli K: Genetic polymorphism of CYP2C19 & therapeutic response to proton pump inhibitors. Indian J Med Res. 127:521–530. 2008.PubMed/NCBI
4	Yin T and Miyata T: Pharmacogenomics of clopidogrel: Evidence and perspectives. Thromb Res. 128:307–316. 2011. View Article : Google Scholar : PubMed/NCBI
5	Blaisdell J, Mohrenweiser H, Jackson J, Ferguson S, Coulter S, Chanas B, Xi T, Ghanayem B and Goldstein JA: Identification and functional characterization of new potentially defective alleles of human CYP2C19. Pharmacogenetics. 12:703–711. 2002. View Article : Google Scholar : PubMed/NCBI
6	Buzoianu AD, Trifa AP, Popp RA, Militaru MS, Militaru CF, Bocşan CI, Farcaş MF and Pop IV: Screening for CYP2C192, 3 and *4 gene variants in a Romanian population study group. Farmacia. 58:806–818. 2010.
7	Beitelshees AL, Horenstein RB, Vesely MR, Mehra MR and Shuldiner AR: Pharmacogenetics and clopidogrel response in patients undergoing percutaneous coronary interventions. Clin Pharmacol Ther. 89:455–459. 2011. View Article : Google Scholar : PubMed/NCBI
8	Scott SA, Sangkuhl K, Gardner EE, Stein CM, Hulot JS, Johnson JA, Roden DM, Klein TE and Shuldiner AR; Clinical Pharmacogenetics Implementation Consortium, : Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450-2C19 (CYP2C19) genotype and clopidogrel therapy. Clin Pharmacol Ther. 90:328–332. 2011. View Article : Google Scholar : PubMed/NCBI
9	Gawrońska-Szklarz B, Adamiak-Giera U, Wyska E, Kurzawski M, Gornik W, Kaldonska M and Drozdzik M: CYP2C19 polymorphism affects single-dose pharmacokinetics of oral pantoprazole in healthy volunteers. Eur J Clin Pharmacol. 68:1267–1274. 2012. View Article : Google Scholar : PubMed/NCBI
10	Sim SC, Risinger C, Dahl ML, Aklillu E, Christensen M, Bertilsson L and Ingelman-Sundberg M: A common novel CYP2C19 gene variant causes ultrarapid drug metabolism relevant for the drug response to proton pump inhibitors and antidepressants. Clin Pharmacol Ther. 79:103–113. 2006. View Article : Google Scholar : PubMed/NCBI
11	Ikebuchi J, Yamada M, Ogura Y, Yamamoto Y, Nishimura A, Nishi K, Yamada K and Irizawa Y: Individual difference in drug metabolism and disposition: Toxicological significance of genotypes and phenotypes of S-mephenytoin 4′-hydroxylase (CYP2C19). Int Congress Series. 1239:589–592. 2003. View Article : Google Scholar
12	Shastry BS: Pharmacogenetics and the concept of individualized medicine. Pharmacogenomics J. 6:16–21. 2005. View Article : Google Scholar
13	Nakamoto K, Kidd JR, Jenison RD, Klaassen CD, Wan YJ, Kidd KK and Zhong XB: Genotyping and haplotyping of CYP2C19 functional alleles on thin-film biosensor chips. Pharmacogenet Genomics. 17:103–114. 2007. View Article : Google Scholar : PubMed/NCBI
14	Sugimoto K, Uno T, Yamazaki H and Tateishi T: Limited frequency of the CYP2C19*17 allele and its minor role in a Japanese population. Br J Clin Pharmacol. 65:437–439. 2008. View Article : Google Scholar : PubMed/NCBI
15	Yamada H, Dahl ML, Lannfelt L, Viitanen M, Winblad B and Sjöqvist F: CYP2D6 and CYP2C19 genotypes in an elderly Swedish population. Eur J Clin Pharmacol. 54:479–481. 1998. View Article : Google Scholar : PubMed/NCBI
16	Brockmöller JJ, Rost K, Gross D, Schenkel A and Roots I: Phenotyping of CYP2C19 with enantiospecific HPLC-quantification of R- and S-mephenytoin and comparison with the intron4/exon5 G->A-splice site mutation. Pharmacogenetics. 5:80–88. 1995.PubMed/NCBI
17	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
18	Dandara C, Masimirembwa CM, Magimba A, Sayi J, Kaaya S, Sommers DK, Snyman JR and Hasler JA: Genetic polymorphism of CYP2D6 and CYP2C19 in east-and southern African populations including psychiatric patients. Eur J Clin Pharmacol. 57:11–17. 2001. View Article : Google Scholar : PubMed/NCBI
19	Goldstein JA, Ishizaki T, Chiba K, de Morais SM, Bell D, Krahn PM and Evans DA: Frequencies of the defective CYP2C19 alleles responsible for the mephenytoin poor metabolizer phenotype in various Oriental, Caucasian, Saudi Arabian and American black populations. Pharmacogenetics. 7:59–64. 1997. View Article : Google Scholar : PubMed/NCBI
20	Sistonen J, Fuselli S, Palo JU, Chauhan N, Padh H and Sajantila A: Pharmacogenetic variation at CYP2C9, CYP2C19, and CYP2D6 at global and microgeographic scales. Pharmacogenet Genomics. 19:170–179. 2009. View Article : Google Scholar : PubMed/NCBI
21	Jurima-Romet M, Goldstein JA, LeBelle M, Aubin RA, Foster BC, Walop W and Rode A: CYP2C19 genotyping and associated mephenytoin hydroxylation polymorphism in a Canadian Inuit population. Pharmacogenetics. 6:329–339. 1996. View Article : Google Scholar : PubMed/NCBI
22	Bathum L, Andersen-Ranberg K, Boldsen J, Brøsen K and Jeune B: Genotypes for the cytochrome P450 enzymes CYP2D6 and CYP2C19 in human longevitY. Role of CYP2D6 and CYP2C19 in longevity. Eur J Clin Pharmacol. 54:427–430. 1998. View Article : Google Scholar : PubMed/NCBI
23	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
24	Hsu HL, Woad KJ, Woodfield DG and Helsby NA: A high incidence of polymorphic CYP2C19 variants in archival blood samples from Papua New Guinea. Hum Genomics. 3:17–23. 2008. View Article : Google Scholar : PubMed/NCBI
25	Blendon RJ, Schoen C, DesRoches C, Osborn R and Zapert K: Common concerns amid diverse systems: Health care experiences in five countries. Health Aff (Millwood). 22:106–121. 2003. View Article : Google Scholar : PubMed/NCBI
26	Lindley CM, Tully MP, Paramsothy V and Tallis RC: Inappropriate medication is a major cause of adverse drug reactions in elderly patients. Age and Ageing. 21:294–300. 1992. View Article : Google Scholar : PubMed/NCBI
27	Pedersen RS, Brasch-Andersen C, Sim SC, Bergmann TK, Halling J, Petersen MS, Weihe P, Edvardsen H, Kristensen VN, Brøsen K and Ingelman-Sundberg M: Linkage disequilibrium between the CYP2C19*17 allele and wildtype CYP2C8 and CYP2C9 alleles: Identification of CYP2C haplotypes in healthy Nordic populations. Eur J Clin Pharmacol. 66:1199–1205. 2010. View Article : Google Scholar : PubMed/NCBI
28	Rudberg I, Mohebi B, Hermann M, Refsum H and Molden E: Impact of the ultrarapid CYP2C19*17 allele on serum concentration of escitalopram in psychiatric patients. Clin Pharmacol Ther. 83:322–327. 2008. View Article : Google Scholar : PubMed/NCBI
29	Kurzawski M, Gawrońska-Szklarz B, Wrześniewska J, Siuda A, Starzyńska T and Droździk M: Effect of CYP2C19*17 gene variant on Helicobacter pylori eradication in peptic ulcer patients. Eur J Clin Pharmacol. 62:877–880. 2006. View Article : Google Scholar : PubMed/NCBI
30	Ruas JL and Lechner MC: Allele frequency of CYP2C19 in a Portuguese population. Pharmacogenetics. 7:333–335. 1997. View Article : Google Scholar : PubMed/NCBI
31	Hoskins JM, Shenfield GM and Gross AS: Relationship between proguanil metabolic ratio and CYP2C19 genotype in a Caucasian population. Br J Clin Pharmacol. 46:499–504. 1998. View Article : Google Scholar : PubMed/NCBI
32	Lamba JK, Dhiman RK and Kohli KK: CYP2C19 genetic mutations in North Indians. Clin Pharmacol Ther. 68:328–335. 2000. View Article : Google Scholar : PubMed/NCBI
33	Ramsjö M, Aklillu E, Bohman L, Ingelman-Sundberg M, Roh HK and Bertilsson L: CYP2C19 activity comparison between Swedes and Koreans: Effect of genotype, sex, oral contraceptive use, and smoking. Eur J Clin Pharmacol. 66:871–877. 2010. View Article : Google Scholar : PubMed/NCBI
34	Kim KA, Song WK, Kim KR and Park JY: Assessment of CYP2C19 genetic polymorphisms in a Korean population using a simultaneous multiplex pyrosequencing method to simultaneously detect the CYP2C192, CYP2C193, and CYP2C19*17 alleles. J Clin Pharm Ther. 35:697–703. 2010. View Article : Google Scholar : PubMed/NCBI
35	Chen L, Qin S, Xie J, Tang J, Yang L, Shen W, Zhao X, Du J, He G and Feng G: 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
36	Kearns GL, Leeder JS and Gaedigk A: Impact of the CYP2C19*17 allele on the pharmacokinetics of omeprazole and pantoprazole in children: Evidence for a differential effect. Drug Metab Dispos. 38:894–897. 2010. View Article : Google Scholar : PubMed/NCBI