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

Clin Appl Thromb Hemost. 2019 Jan-Dec:25:1076029619875520. doi: 10.1177/1076029619875520.

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.

Keywords: clopidogrel resistance; gain-of-function allele; genetic; loss-of-function allele.

Publication types

  • Systematic Review

MeSH terms

  • Africa, Northern
  • Alleles
  • Clopidogrel / pharmacology*
  • Cytochrome P-450 CYP2C19 / adverse effects
  • Cytochrome P-450 CYP2C19 / genetics*
  • Drug Resistance / genetics
  • Humans
  • Loss of Function Mutation
  • Middle East
  • Observational Studies as Topic
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Aggregation Inhibitors / therapeutic use

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19