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LETTER TO THE EDITOR
Year : 2021  |  Volume : 53  |  Issue : 1  |  Page : 85-87
 

The CYP2C19 genotypes and its effect on clopidogrel as an anti-platelet drug among the Arab population


1 Department of Biomedical Sciences, College of Veterinary Medicine, King Faisal University, Al-Hofuf, Al-Ahsa; Department of Research and Development, Chronic Disease Prevention Center, Ministry of Health, Riyadh, Saudi Arabia
2 Department of Research and Development, Chronic Disease Prevention Center, Ministry of Health, Riyadh, Saudi Arabia
3 Department of Pharmacy, King Khaled University Hospital, Medical City King Saud University, Riyadh, Saudi Arabia
4 Department of Sales, Fresenius Kabi, Alhaya Medical Company, Dammam, Saudi Arabia
5 Department of General Medicine, Faculty of Medicine, Imam Abdulrahman bin Faisal University, Dammam, Saudi Arabia

Date of Submission24-Aug-2020
Date of Decision26-Dec-2020
Date of Acceptance18-Mar-2021
Date of Web Publication28-Apr-2021

Correspondence Address:
Dr. Abdullah Alkattan
Department of Biomedical Sciences, College of Veterinary Medicine, King Faisal University, Al-Hofuf, 31982 Al-Ahsa
Saudi Arabia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijp.IJP_690_20

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How to cite this article:
Alkattan A, Almutairi Y, Alsalameen E, Alkhalifah A, Alghanim F. The CYP2C19 genotypes and its effect on clopidogrel as an anti-platelet drug among the Arab population. Indian J Pharmacol 2021;53:85-7

How to cite this URL:
Alkattan A, Almutairi Y, Alsalameen E, Alkhalifah A, Alghanim F. The CYP2C19 genotypes and its effect on clopidogrel as an anti-platelet drug among the Arab population. Indian J Pharmacol [serial online] 2021 [cited 2021 May 15];53:85-7. Available from: https://www.ijp-online.com/text.asp?2021/53/1/85/315085




Sir,

Patients with cardiovascular diseases (CVDs) include stroke, coronary artery disease, deep-vein thrombosis, and pulmonary embolism are at high risk of recurrent cardiovascular events (CVEs), because of that, it is necessary to prevent further coagulations for those patients.[1] Many antiplatelet and anticoagulant drugs had been studied about their safety and efficacy on patients with CVDs to prevent recurrent CVEs in future.[2]

Clopidogrel is a common anti-platelet drug used as prophylaxis to protect patients with previous coronary artery thrombosis from recurrent CVEs.[3] Clopidogrel depends on various cytochrome P450 enzymes (CYP450) to be converted to its active metabolite. These enzymes include CYP3A4, CYP1A2, CYP2C19, CYP2C9, and CYP2B6. CYP2C19 enzyme is one of the important factors related to the clopidogrel activation process, and any mutation of the CYP2C19 gene could decrease the anti-platelet activity of clopidogrel.[4]

Seven articles[5],[6],[7],[8],[9],[10],[11] reported data for the CYP2C19 gene variation among Arab people, and some of these articles correlate the gene variations with clopidogrel anti-platelets activity. Eight hundred and sixty-two participants were genotyped in order to determine the CYP2C19 gene status among the Arab populations including Saudis, Egyptians, Jordanians, Lebanese, and Tunisians people. There were 197 participants (22.85%) carrying CYP2C19*2 allele, 230 participants (26.68%) carrying CYP2C19*17 allele and few participants (1.04%) were carrying CYP2C19*3 allele. The mean ADP-induced platelet activation (AIPA) among participants that carrying two wild-type alleles of the CYP2C19 gene was 37.1% ± 23% and was 63.2% ± 33% and 58.29% ± 28% among CYP2C19*2 allele and CYP2C19*3 carriers, respectively.

The most frequent CYP2C19 genotypes found among Arab people were (*1/*1), (*1/*17), (*1/*2), (*2/*2), (*17/*17), (*3/*3) and (*1/*3), respectively [Figure 1]. The AIPA levels were elevated among patients with (*1/*2), (*2/*2), (*3/*3), and (*1/*3) genotypes compared with patients with other genotypes, and the AIPA levels differences between them were significant.

The frequency of CYP2C19 (*1/*1) genotype was high as expected; of which 49.4% of the Arab participants included in this study were carrying two wild-type alleles of CYP2C19 gene, thus (*1/*1) genotype described as the most frequent genotype among Arab people. The second most frequent genotype distributed among Arabs was the (*1/*17) genotype; in which 21.2% of the participants carrying this genotype in their genetic makeup. Moreover, CYP2C19 (*1/*2) genotype frequency among Arab participants was 16.7%; which was regarded as the third most frequent genotype among Arab participants. The other highly frequent genotypes among Arab participants including (*2/*2), (*17/*17), (*3/*3), and (*1/*3) with the percentages 6.14%, 5.45%, 0.7%, and 0.35%, respectively.
Figure 1: Different CYP2C19 genotypes frequencies among Arab people

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Based on different CYP2C19 genotypes frequencies data, the most frequent CYP2C19 phenotype among Arab people was the normal CYP2C19 enzyme activity (NCEA); of which 49.4% have this phenotype. Other very common CYP2C19 phenotypes among Arab people include potent CYP2C19 enzyme activity (PCEA) and low CYP2C19 enzyme activity (LCEA) with percentages of 21.2% and 17.05%, respectively.

Nevertheless, some CYP2C19 phenotypes were described as common phenotypes among Arab participants including inactive CYP2C19 enzyme (ICE) and very PCEA (VPCEA) with percentages of 6.84% and 5.45%, respectively. There were significant differences between the NCEA phenotype compared with other phenotypes frequencies related to the CYP2C19 gene (P < 0.0001). Moreover, there were significant differences between PCEA phenotype compared with ICE and VPCEA phenotypes frequencies (P < 0.0001), and also there were significant differences between LCEA phenotype compared with ICE and VPCEA phenotypes frequencies (P < 0.0001). However, there was no significant difference between PCEA and LCEA phenotype frequencies (P > 0.05), and there was no significant difference between ICE and VPCEA phenotype frequencies (P > 0.05).


  Conclusions Top


  • CYP2C19 genotypes include (*1/*1), (*1/*2), (*1/*3), (*1/*17), (*2/*2), (*3/*3), and (*17/*17) are distributed among Arab population
  • The AIPA levels were elevated among clopidogrel users with LCEA/ICE phenotypes compared with patients with NCEA phenotype, and the AIPA levels differences between them were significant
  • The most frequent CYP2C19 genotypes found among Arab people are (*1/*1), (*1/*17), (*1/*2), (*2/*2), (*17/*17), (*3/*3), and (*1/*3), respectively
  • The most frequent CYP2C19 phenotypes found among Arab people are NCEA, PCEA, LCEA, ICE, and VPCEA, respectively.


Recommendations

  • Arab patients with CVDs should do CYP2C19 genotyping tests when considering clopidogrel anti-platelet therapy for them
  • Arab patients who have (*1/*1), (*1/*17) or (*17/*17) genotype could use clopidogrel 75 mg as a maintenance dose, unless if they have any contraindication for clopidogrel
  • Arab patients who have (*1/*2), (*1/*3), (*2/*2), or (*3/*3) genotype should not use clopidogrel as prophylaxis for CVDs
  • Patients should be advised to not taking clopidogrel with omeprazole, esomeprazole, lansoprazole, or dexlansoprazole at the same time, and should separate taking them by at least 6–12 h
  • Patients should be advised to not taking clopidogrel with CYP2C19 enzyme inhibitors (e.g., ketoconazole, fluconazole, fluoxetine, fluvoxamine, oxcarbazepine, topiramate, and isoniazid).


Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Malaguarnera G, Latteri S, Catania VE, Malaguarnera M. Reduction of cardiovascular risk in subjects with high lipoprotein (a) levels. J Thorac Dis 2017;9:2332-6.  Back to cited text no. 1
    
2.
Gradolí J, Vidal V, Brady AJ, Facila L. Anticoagulation in patients with ischaemic heart disease and peripheral arterial disease: clinical implications of COMPASS study. Eur Cardiol 2018;13:115-8.  Back to cited text no. 2
    
3.
Damman P, Woudstra P, Kuijt WJ, de Winter RJ, James SK. P2Y12 platelet inhibition in clinical practice. J Thromb Thrombolysis 2012;33:143-53.  Back to cited text no. 3
    
4.
Frelinger AL 3rd, Bhatt DL, Lee RD, Mulford DJ, Wu J, Nudurupati S, et al. Clopidogrel pharmacokinetics and pharmacodynamics vary widely despite exclusion or control of polymorphisms (CYP2C19, ABCB1, PON1), noncompliance, diet, smoking, co-medications (including proton pump inhibitors), and pre-existent variability in platelet function. J Am Coll Cardiol 2013;61:872-9.  Back to cited text no. 4
    
5.
Al-Jenoobi FI, Alkharfy KM, Alghamdi AM, Bagulb KM, Al-Mohizea AM, Al-Muhsen S, et al. CYP2C19 genetic polymorphism in Saudi Arabians. Basic Clin Pharmacol Toxicol 2013;112:50-4.  Back to cited text no. 5
    
6.
Alhazzani AA, Munisamy M, Karunakaran G. Pharmacogenetics of CYP2C19 genetic polymorphism on clopidogrel response in patients with ischemic stroke from Saudi Arabia. Neurosciences (Riyadh, Saudi Arabia) 2017;22:31-7.  Back to cited text no. 6
    
7.
Khalaf H, Al Meman AA, 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;10:65-70.  Back to cited text no. 7
    
8.
Khalil BM, Shahin MH, Solayman MH, Langaee T, Schaalan MF, Gong Y, et al. Genetic and nongenetic factors affecting clopidogrel response in the Egyptian population. Clin Transl Sci 2016;9:23-8.  Back to cited text no. 8
    
9.
Rjoub M, Saleh A, Hakooz N, Imraish A, Jarrar Y, Zihlif M. Allelic frequency of PON1 Q192R, CYP2C19*2 and CYP2C19*17 among Jordanian patients taking clopidogrel. Trop J Pharm Res 2018; 17:2275-80.  Back to cited text no. 9
    
10.
Ahmad M, Navarro-Quiroz E, García Moreno AM, Rios Anillo MR, Silvera Redondo CA, Fernandez Ponce C. Analysis of Gene Polymorphism CYP2C19 in the Lebanese Population Who Reside in Colombia. Global Journal of Health Science 2018; 10:36-42.  Back to cited text no. 10
    
11.
Abid L, Laroussi L, Bahloul A, Siala A, Abdelhédi R, Kharrat N, et al. Impact of cytochrome P450 2C19*2 polymorphism on the clinical cardiovascular events after stent implantation in patients receiving clopidogrel of a southern Tunisian region. World Journal of Cardiovascular Diseases 2013;3:4-10. doi: 10.4236/wjcd.2013.31002.  Back to cited text no. 11
    


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