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Drug Metabolism Letters

Editor-in-Chief

ISSN (Print): 1872-3128
ISSN (Online): 1874-0758

Systematic Review Article

Major CYP450 Polymorphism among Saudi Patients

Author(s): Ahmad A. Almeman*

Volume 14, Issue 1, 2021

Published on: 22 July, 2020

Page: [17 - 24] Pages: 8

DOI: 10.2174/1872312814666200722122232

Price: $65

Abstract

Background: Cytochrome P450 (CYP) contributes to a huge collection of medicinal products' Phase I metabolization. We aimed to summarize and investigate the current evidence regarding the frequency of CYP2D6, CYP2C9, CYP2C19, and MDR1 in Saudi Arabia.

Methods: A computerized search in four databases was done using the relevant keywords. The screening process was done in two steps; title and abstract screening and full-text screening. Data of demographic and characteristics of included studies and patients were extracted and tabulated.

Results: Ten studies were eligible for our criteria and were included in this systematic review. The age of participants ranged between 17-65 years. Only two subjects showed PM phenotype of CYP2C19 in the Saudi population. The most frequent alleles were CYP2C19*1 (62.9%), CYP2C19*2 (11.2%-32%), and CYP2C19*17 (25.7%). The CYP2C19m1 was observed in 97 cases of extensive metabolizing (EM) phenotype CYP2C19. Concerning the CYP2C9, the most frequent alleles were CYP2C9*1 and CYP2C9*2, and the most frequent genotype was CYP2C9*1*1. The CYP2D6*41 allele and C1236T MDR1 were the most frequent allele in this population.

Conclusion: The current evidence suggests that Saudi resembled European in the frequency of CYP2C19, Caucasians in both the incidence of CYP2C9 and CYP2C19m1, and the absence of CYP2C19m2. The CYP2D6*41 allele frequency in Saudi is relatively high. We recommend further research to evaluate the basic and clinical relevance of gene polymorphism in such ethnicity.

Keywords: CYP2C19, CYP2C9, CYP2D6, MDR1, polymorphism, Saudis, Cytochrome P450 (CYP).

Graphical Abstract
[1]
Jiang, X-L.; Samant, S.; Lesko, L.J.; Schmidt, S. Clinical pharmacokinetics and pharmacodynamics of clopidogrel. Clin. Pharmacokinet., 2015, 54(2), 147-166.
[http://dx.doi.org/10.1007/s40262-014-0230-6 ] [PMID: 25559342]
[2]
Alomar, M.J. Factors affecting the development of adverse drug reactions. Saudi Pharm. J., 2014, 22(2), 83-94.
[http://dx.doi.org/10.1016/j.jsps.2013.02.003 ] [PMID: 24648818]
[3]
Madian, A.G.; Wheeler, H.E.; Jones, R.B.; Dolan, M.E. Relating human genetic variation to variation in drug responses. Trends Genet., 2012, 28(10), 487-495.
[http://dx.doi.org/10.1016/j.tig.2012.06.008 ] [PMID: 22840197]
[4]
Roden, D.M.; Wilke, R.A.; Kroemer, H.K.; Stein, C.M. Pharmacogenomics: The genetics of variable drug responses. Circulation, 2011, 123(15), 1661-1670.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.109.914820 ] [PMID: 21502584]
[5]
Zhou, S-F.; Di, Y.M.; Chan, E.; Du, Y.M.; Chow, V.D-W.; Xue, C.C.; Lai, X.; Wang, J-C.; Li, C.G.; Tian, M.; Duan, W. Clinical pharmacogenetics and potential application in personalized medicine. Curr. Drug Metab., 2008, 9(8), 738-784.
[http://dx.doi.org/10.2174/138920008786049302 ] [PMID: 18855611]
[6]
Zanger, U.M.; Schwab, M. Cytochrome P450 enzymes in drug metabolism: Regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol. Ther., 2013, 138(1), 103-141.
[http://dx.doi.org/10.1016/j.pharmthera.2012.12.007 ] [PMID: 23333322]
[7]
Scott, S.A.; Sangkuhl, K.; Shuldiner, A.R.; Hulot, J.S.; Thorn, C.F.; Altman, R.B.; Klein, T.E. PharmGKB summary: Very important pharmacogene information for cytochrome P450, family 2, subfamily C, polypeptide 19. Pharmacogenet. Genomics, 2012, 22(2), 159-165.
[http://dx.doi.org/10.1097/FPC.0b013e32834d4962 ] [PMID: 22027650]
[8]
Läpple, F.; von Richter, O.; Fromm, M.F.; Richter, T.; Thon, K.P.; Wisser, H.; Griese, E-U.; Eichelbaum, M.; Kivistö, K.T. Differential expression and function of CYP2C isoforms in human intestine and liver. Pharmacogenetics, 2003, 13(9), 565-575.
[http://dx.doi.org/10.1097/00008571-200309000-00005 ] [PMID: 12972955]
[9]
Daly, A.K.; Rettie, A.E.; Fowler, D.M.; Miners, J.O. Pharmacogenomics of CYP2C9: Functional and clinical considerations. J. Pers. Med., 2017, 8(1), 1.
[http://dx.doi.org/10.3390/jpm8010001 ] [PMID: 29283396]
[10]
Dong, Y.; Xiao, H.; Wang, Q.; Zhang, C.; Liu, X.; Yao, N.; Sheng, H.; Li, H. Analysis of genetic variations in CYP2C9, CYP2C19, CYP2D6 and CYP3A5 genes using oligonucleotide microarray. Int. J. Clin. Exp. Med., 2015, 8(10), 18917-18926.
[PMID: 26770516]
[11]
Cavallari, L.H.; Franchi, F.; Rollini, F.; Been, L.; Rivas, A.; Agarwal, M.; Smith, D.M.; Newsom, K.; Gong, Y.; Elsey, A.R.; Starostik, P.; Johnson, J.A.; Angiolillo, D.J. Clinical implementation of rapid CYP2C19 genotyping to guide antiplatelet therapy after percutaneous coronary intervention. J. Transl. Med., 2018, 16(1), 92.
[http://dx.doi.org/10.1186/s12967-018-1469-8 ] [PMID: 29642909]
[12]
Brown, S-A.; Pereira, N. Pharmacogenomic impact of CYP2C19 variation on clopidogrel therapy in precision cardiovascular medicine. J. Pers. Med., 2018, 8(1), 8.
[http://dx.doi.org/10.3390/jpm8010008 ] [PMID: 29385765]
[13]
Zhou, S-F.; Liu, J-P.; Lai, X-S. Substrate specificity, inhibitors and regulation of human cytochrome P450 2D6 and implications in drug development. Curr. Med. Chem., 2009, 16(21), 2661-2805.
[http://dx.doi.org/10.2174/092986709788681985 ] [PMID: 19601803]
[14]
Chan, W.; Li, M.S.; Sundaram, S.K.; Tomlinson, B.; Cheung, P.Y.; Tzang, C.H. CYP2D6 allele frequencies, copy number variants, and tandems in the population of Hong Kong. J. Clin. Lab. Anal., 2019, 33(1)e22634
[http://dx.doi.org/10.1002/jcla.22634 ] [PMID: 30069923]
[15]
Pinto, N.; Dolan, M.E. Clinically relevant genetic variations in drug metabolizing enzymes. Curr. Drug Metab., 2011, 12(5), 487-497.
[http://dx.doi.org/10.2174/138920011795495321 ] [PMID: 21453273]
[16]
Del Tredici, A.L.; Malhotra, A.; Dedek, M.; Espin, F.; Roach, D.; Zhu, G.D.; Voland, J.; Moreno, T.A. Frequency of CYP2D6 alleles including structural variants in the United States. Front. Pharmacol., 2018, 9, 305.
[http://dx.doi.org/10.3389/fphar.2018.00305 ] [PMID: 29674966]
[17]
Al-Mohizea, A.M.; Alkharfy, K.M.; Bagulb, K.M.; Alghamdi, A.M.; Al-Jenoobi, F.I.; Al-Muhsen, S.; Halwani, R.; Parvez, M.K.; Al-Dosari, M.S. Genetic variability and haplotype profile of MDR1 in Saudi Arabian males. Mol. Biol. Rep., 2012, 39(12), 10293-10301.
[http://dx.doi.org/10.1007/s11033-012-1906-3 ] [PMID: 23053935]
[18]
Evans, D.A.; Krahn, P.; Narayanan, N. The mephenytoin (cytochrome P450 2C 19) and dextromethorphan (cytochrome P450 2D6) polymorphisms in Saudi Arabians and Filipinos. Pharmacogenetics, 1995, 5(2), 64-71.
[http://dx.doi.org/10.1097/00008571-199504000-00002 ] [PMID: 7663530]
[19]
Saeed, L.H.; Mayet, A.Y. Genotype-phenotype analysis of CYP2C19 in healthy saudi individuals and its potential clinical implication in drug therapy. Int. J. Med. Sci., 2013, 10(11), 1497-1502.
[http://dx.doi.org/10.7150/ijms.6795 ] [PMID: 24046523]
[20]
Goldstein, J.A.; Ishizaki, T.; Chiba, K.; de Morais, S.M.; Bell, D.; Krahn, P.M.; Evans, D.A. Frequencies of the defective CYP2C19 alleles responsible for the mephenytoin poor metabolizer phenotype in various Oriental, Caucasian, Saudi Arabian and American black populations. Pharmacogenetics, 1997, 7(1), 59-64.
[http://dx.doi.org/10.1097/00008571-199702000-00008 ] [PMID: 9110363]
[21]
Liberati, A.; Altman, D.G.; Tetzlaff, J.; Mulrow, C.; Gøtzsche, P.C.; Ioannidis, J.P.A.; Clarke, M.; Devereaux, P.J.; Kleijnen, J.; Moher, D. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J. Clin. Epidemiol., 2009, 62(10), e1-e34.
[http://dx.doi.org/10.1016/j.jclinepi.2009.06.006 ] [PMID: 19631507]
[22]
McLellan, R.A.; Oscarson, M.; Seidegård, J.; Evans, D.A.; Ingelman-Sundberg, M. Frequent occurrence of CYP2D6 gene duplication in Saudi Arabians. Pharmacogenetics, 1997, 7(3), 187-191.
[http://dx.doi.org/10.1097/00008571-199706000-00003 ] [PMID: 9241658]
[23]
Mirghani, R.A.; Chowdhary, G.; Elghazali, G. Distribution of the major cytochrome P450 (CYP) 2C9 genetic variants in a Saudi population. Basic Clin. Pharmacol. Toxicol., 2011, 109(2), 111-114.
[http://dx.doi.org/10.1111/j.1742-7843.2011.00692.x ] [PMID: 21371265]
[24]
Al-Dosari, M.S.; Al-Jenoobi, F.I.; Alkharfy, K.M.; Alghamdi, A.M.; Bagulb, K.M.; Parvez, M.K.; Al-Mohizea, A.M.; Al-Muhsen, S.; Halwani, R. High prevalence of CYP2D6*41 (G2988A) allele in Saudi Arabians. Environ. Toxicol. Pharmacol., 2013, 36(3), 1063-1067.
[http://dx.doi.org/10.1016/j.etap.2013.09.008 ] [PMID: 24121619]
[25]
Alsaif, A.A.; Hasan, T.N.; Shafi, G.; Syed, N.A.; Alsaif, M.A.; Al-Assaf, A.H.; Alshatwi, A.A. Association of multiple drug resistance-1 gene polymorphism with multiple drug resistance in breast cancer patients from an ethnic Saudi Arabian population. Cancer Epidemiol., 2013, 37(5), 762-766.
[http://dx.doi.org/10.1016/j.canep.2013.04.011 ] [PMID: 23725642]
[26]
Alzahrani, A.M.; Ragia, G.; Hanieh, H.; Manolopoulos, V.G. Genotyping of CYP2C9 and VKORC1 in the Arabic population of Al-Ahsa, Saudi Arabia. BioMed Res. Int., 2013.2013315980
[http://dx.doi.org/10.1155/2013/315980 ] [PMID: 23586031]
[27]
Khalaf, H.; Al Meman, A.A.; Rasool, S. AbdulRahman Al Meman, A.; Rasool, S. Impact of cytochrome P450 2C19*2 and *3 on clopidogrel loading dose in Saudi patients with acute coronary syndrome. Drug Metab. Lett., 2016, 10(1), 65-70.
[http://dx.doi.org/10.2174/1872312810666151117122841 ] [PMID: 26573281]
[28]
LLerena, A.; Herraíz, A.G.; Cobaleda, J.; Johansson, I.; Dahl, M.L. Debrisoquin and mephenytoin hydroxylation phenotypes and CYP2D6 genotype in patients treated with neuroleptic and antidepressant agents. Clin. Pharmacol. Ther., 1993, 54(6), 606-611.
[http://dx.doi.org/10.1038/clpt.1993.197 ] [PMID: 7903915]
[29]
Breimer, D.D.; Vermeulen, N.P.; Danhof, M.; Teunissen, M.; Joeres, R.P.; van der Graaff, M. Assessment and Prediction of In Vivo Oxidative Drug Metabolizing Activity. In: Benet L.Z Levy G. Ferraiolo B.L. (eds) Pharmacokinetics. Springer, Boston, MA; 191-216.
[http://dx.doi.org/10.1007/978-1-4613-2799-8_17]
[30]
Bertilsson, L.; Lou, Y.Q.; Du, Y.L.; Liu, Y.; Kuang, T.Y.; Liao, X.M.; Wang, K.Y.; Reviriego, J.; Iselius, L.; Sjöqvist, F. Pronounced differences between native Chinese and Swedish populations in the polymorphic hydroxylations of debrisoquin and S-mephenytoin. Clin. Pharmacol. Ther., 1992, 51(4), 388-397.
[http://dx.doi.org/10.1038/clpt.1992.38 ] [PMID: 1345344]
[31]
Mahgoub, A.; Idle, J.R.; Smith, R.L. A population and familial study of the defective alicyclic hydroxylation of debrisoquine among Egyptians. Xenobiotica, 1979, 9(1), 51-56.
[http://dx.doi.org/10.3109/00498257909034703 ] [PMID: 760321]
[32]
Bertilsson, L. Geographical/interracial differences in polymorphic drug oxidation. Current state of knowledge of cytochromes P450 (CYP) 2D6 and 2C19. Clin. Pharmacokinet., 1995, 29(3), 192-209.
[http://dx.doi.org/10.2165/00003088-199529030-00005 ] [PMID: 8521680]
[33]
Bahbah, E.; Abdalla, A.R.; Abdelshafy, K.; Almohandes, A.D.; Menshawy, A.; Aziz, M.A.E.; Ebada, M.A.; Hegab, A.; Negida, A. Should olanzapine be advocated over conventional anti-emetics for the prevention of chemotherapy-induced nausea and vomiting? An updated meta-analysis of randomized control trials. Curr. Enzym. Inhib., 2019, 15, 1-11.
[http://dx.doi.org/10.2174/1573408015666190620165507]
[34]
Xiong, S.; Li, L. The effect of CYP1A2 gene polymorphism on the metabolism of theophylline. Exp. Ther. Med., 2018, 15(1), 109-114.
[PMID: 29387184]
[35]
Al-Ahmad, M.M.; Amir, N.; Dhanasekaran, S.; John, A.; Abdulrazzaq, Y.M.; Ali, B.R.; Bastaki, S.M.A. Genetic polymorphisms of cytochrome P450-1A2 (CYP1A2) among Emiratis. PLoS One, 2017, 12(9)e0183424
[http://dx.doi.org/10.1371/journal.pone.0183424 ] [PMID: 28934216]
[36]
Johar, D.; Ahmed, S.M.; El Hayek, S.; Al-Dewik, N.; Bahbah, E.I.; Omar, N.H.; Mustafa, M.; Salman, D.O.; Fahmey, A.; Mottawea, M.; Azouz, R.A.M.; Bernstein, L. Diabetes-induced proteome changes throughout development. Endocr. Metab. Immune Disord. Drug Targets, 2019, 19(6), 732-743.
[http://dx.doi.org/10.2174/1871530319666190305153810 ] [PMID: 31038056]
[37]
Božina, N.; Bradamante, V.; Lovrić, M. Genetic polymorphism of metabolic enzymes P450 (CYP) as a susceptibility factor for drug response, toxicity, and cancer risk. Arh. Hig. Rada Toksikol., 2009, 60(2), 217-242.
[http://dx.doi.org/10.2478/10004-1254-60-2009-1885 ] [PMID: 19581216]
[38]
Qin, S.; Shen, L.; Zhang, A.; Xie, J.; Shen, W.; Chen, L.; Tang, J.; Xiong, Y.; Yang, L.; Shi, Y.; Feng, G.; He, L.; Xing, Q. Systematic polymorphism analysis of the CYP2D6 gene in four different geographical Han populations in mainland China. Genomics, 2008, 92(3), 152-158.
[http://dx.doi.org/10.1016/j.ygeno.2008.05.004 ] [PMID: 18632250]
[39]
Sosa-Macías, M.; Dorado, P.; Alanis-Bañuelos, R.E.; Llerena, A.; Lares-Asseff, I. Influence of CYP2D6 deletion, multiplication, -1584C-->G, 31G-->A and 2988G-->a gene polymorphisms on dextromethorphan metabolism among Mexican tepehuanos and mestizos. Pharmacology, 2010, 86(1), 30-36.
[http://dx.doi.org/10.1159/000314334 ] [PMID: 20588073]
[40]
Toscano, C.; Klein, K.; Blievernicht, J.; Schaeffeler, E.; Saussele, T.; Raimundo, S.; Eichelbaum, M.; Schwab, M.; Zanger, U.M. Impaired expression of CYP2D6 in intermediate metabolizers carrying the *41 allele caused by the intronic SNP 2988G>A: Evidence for modulation of splicing events. Pharmacogenet. Genomics, 2006, 16(10), 755-766.
[http://dx.doi.org/10.1097/01.fpc.0000230112.96086.e0 ] [PMID: 17001295]
[41]
Tanira, M.O.; Al-Mukhaini, M.K.; Al-Hinai, A.T.; Al Balushi, K.A.; Ahmed, I.S. Frequency of CYP2C9 genotypes among Omani patients receiving warfarin and its correlation with warfarin dose. Community Genet., 2007, 10(1), 32-37.
[http://dx.doi.org/10.1159/000096279 ] [PMID: 17167248]
[42]
Pilotto, A.; Seripa, D.; Franceschi, M.; Scarcelli, C.; Colaizzo, D.; Grandone, E.; Niro, V.; Andriulli, A.; Leandro, G.; Di Mario, F.; Dallapiccola, B. Genetic susceptibility to nonsteroidal anti-inflammatory drug-related gastroduodenal bleeding: Role of cytochrome P450 2C9 polymorphisms. Gastroenterology, 2007, 133(2), 465-471.
[http://dx.doi.org/10.1053/j.gastro.2007.05.025 ] [PMID: 17681167]
[43]
Tan, G-M.; Wu, E.; Lam, Y-Y.; Yan, B.P. Role of warfarin pharmacogenetic testing in clinical practice. Pharmacogenomics, 2010, 11(3), 439-448.
[http://dx.doi.org/10.2217/pgs.10.8 ] [PMID: 20402581]

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