The Effect of CYP2C19 and Nongenetic Factors on Clopidogrel Responsiveness in the MENA Region: A Systematic Review

Abstract

Clopidogrel is the cornerstone antiplatelet used in the treatment and prevention of thrombotic events. Some studies examined the effect of CYP2C19 polymorphism and nongenetic factors on clopidogrel response in the Middle East and North Africa (MENA) region. However, the consistency among these studies is yet unknown. This study aims to estimate the prevalence of CYP2C19 genetic variants in MENA region and to evaluate the effect of these variants as well as the nongenetic factors on clopidogrel responsiveness. A systematic literature search was performed to identify relevant articles. Only observational studies were included. A total of 20 studies in 8 different populations were included. The CYP2C19*2 variant is the most prevalent loss-of-function (LOF) allele in the MENA region (1.7%-35%). The frequency of CYP2C19*17 ranged from 5.3% to 26.9%. Of the 9 studies, 6 found an association between carriers of at least 1 LOF allele and clopidogrel resistance. Older age, high body mass index, females, and the use of calcium channel blockers were associated with clopidogrel resistance as well. Association between the CYP2C19*2 allele and clopidogrel resistance is common among MENA populations. Future studies should focus on having larger sample sizes to detect other minor variant alleles and their effect on bleeding and cardiovascular outcomes.

A review of pharmacogenomics studies assessing the knowledge and attitudes of physicians and pharmacists across the Arab and Middle Eastern Region

“…This is because there has been continuous migration in and out of the countries in this region leading to a mixed population of different ethnicity such as Arab, Asian, African, and Caucasian. 53 In Jordan a study included 128 pharmacists in which their knowledge scores were measured, the outcome is quite similar to previously mentioned studies where they also scored very low in regard to their knowledge, yet they showed high motivation in implementing it. Almost half of the participant answered PGx could be related to their profession.…”

Variation in 100 relevant pharmacogenes among emiratis with insights from understudied populations

“…In the current group important variants with multiple interactions were detected in CYP2C19 , including rs4244285. This variant has been reported with high prevalence in the populations from the Middle East 51 . This allele interacts with clopidogrel and with many antidepressants, which some of them are also substrates to CYP2D6 .…”

“…The interaction of these two genes and their effect on antidepressants are important pharmacogenomic interactions that warrant further evaluation. Nevertheless the limited study numbers and sizes that have ever evaluated CYP2C19 alleles in participants rather than Caucasians [50][51][52] .…”

The Impact of Kinase Insert Domain (KDR) Gene Polymorphism rs2305948 on Clopidogrel Resistance in Iraqi Patients Undergoing Elective Percutaneous Coronary Intervention (PCI)

“…Clopidogrel antiplatelet activity has been evaluated by many studies trying to explain the poor response in inhibiting platelet aggregation through the effect of gene single nucleotide polymorphism of the activating enzyme CYP2C19 ( 27 ). Additionally, there are other important contributing factors such as drug interaction ( 28 ), epigenetic factor, disease and demographic factors ( 29 ). Recently, there has been large concern and orientation in scientific researches towards genetic single nucleotide polymorphism as an effective contributor behind diminished activity of clopidogrel in inhibiting platelet aggregation ( 30 ).…”