Dataset Information

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.

SUBMITTER: Ali Z

PROVIDER: S-EPMC6829969 | biostudies-literature | 2019 Jan-Dec

REPOSITORIES: biostudies-literature

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

Ali Zainab Z Elewa Hazem H

Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis 20190101

Clopidogrel is the cornerstone antiplatelet used in the treatment and prevention of thrombotic events. Some studies examined the effect of <i>CYP2C19</i> 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 <i>CYP2C19</i> genetic variants in MENA region and to evaluate the effect of these variants as well as the nongenetic factors on ...[more]

PMID: 31512486

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Project description:BackgroundWarfarin is the most commonly used oral anticoagulant for the treatment and prevention of thromboembolic disorders. Pharmacogenomics studies have shown that variants in CYP2C9 and VKORC1 genes are strongly and consistently associated with warfarin dose variability. Although different populations from the Middle East and North Africa (MENA) region may share the same ancestry, it is still unclear how they compare in the genetic and non-genetic factors affecting their warfarin dosing.ObjectiveTo explore the prevalence of CYP2C9 and VKORC1 variants in MENA, and the effect of these variants along with other non-genetic factors in predicting warfarin dose.MethodsIn this systematic review, we included observational cross sectional and cohort studies that enrolled patients on stable warfarin dose and had the genetics and non-genetics factors associated with mean warfarin dose as the primary outcome. We searched PubMed, Medline, Scopus, PharmGKB, PHGKB, Google scholar and reference lists of relevant reviews.ResultsWe identified 17 studies in eight different populations: Iranian, Israeli, Egyptian, Lebanese, Omani, Kuwaiti, Sudanese and Turkish. Most common genetic variant in all populations was the VKORC1 (-1639G>A), with a minor allele frequency ranging from 30% in Egyptians and up to 52% and 56% in Lebanese and Iranian, respectively. Variants in the CYP2C9 were less common, with the highest MAF for CYP2C9*2 among Iranians (27%). Variants in the VKORC1 and CYP2C9 were the most significant predictors of warfarin dose in all populations. Along with other genetic and non-genetic factors, they explained up to 63% of the dose variability in Omani and Israeli patients.ConclusionVariants of VKORC1 and CYP2C9 are the strongest predictors of warfarin dose variability among the different populations from MENA. Although many of those populations share the same ancestry and are similar in their warfarin dose predictors, a population specific dosing algorithm is needed for the prospective estimation of warfarin dose.

Project description:ObjectiveTo evaluate the accumulated information from genetic association studies investigating the impact of variants of the cytochrome P450 (CYP) 2C19 genotype on the clinical efficacy of clopidogrel.DesignSystematic review and meta-analysis with a structured search algorithm and prespecified eligibility criteria for retrieval of relevant studies; dominant genetic model assumptions and quantitative methods for calculating summary effect estimates from study level odds ratios; systematic assessment of bias within and between studies; and grading of the cumulative evidence by consensus criteria.Data sourcesMedline, Embase, the Cochrane Library, online databases, contents pages and bibliographies of general medical, cardiovascular, pharmacological, and genetic journals. Eligibility criteria for selecting studies Original full length reports assessing the cumulative incidence of major adverse cardiovascular events or stent thrombosis over a follow-up period of at least a month in association with carrier status for the loss of function or gain of function CYP2C19 allele in adult patients with coronary artery disease and a clinical presentation of acute coronary syndrome or stable angina pectoris who were taking clopidogrel.Results15 studies met the inclusion criteria. The random effects summary odds ratio for stent thrombosis in carriers of at least one CYP2C19 loss of function allele versus non-carriers combining nine studies was 1.77 (95% confidence interval 1.31 to 2.40; P < 0.001). This nominally significant odds ratio was subject to considerable bias across the studies (small study effect bias and replication diversity). The adjustment for these quality modifiers tended to abolish the association. The corresponding random effects summary odds ratio of major adverse cardiovascular events for 12 studies combined was 1.11 (0.89 to 1.39; P = 0.36). The random effects summary odds ratio of stent thrombosis in carriers versus non-carriers of at least one CYP2C19*17 gain of function allele for three studies combined was 0.99 (0.60 to 1.62; P = 0.96), and the corresponding odds ratio of major adverse cardiovascular events in five studies was 0.93 (0.75 to 1.14; P = 0.48). The overall quality of epidemiological evidence was graded as low, which excludes reliable clinical assessments.ConclusionsAccumulated information from genetic association studies does not indicate a substantial or consistent influence of CYP2C19 gene polymorphisms on the clinical efficacy of clopidogrel. The current evidence does not support the use of individualised antiplatelet regimens guided by CYP2C19 genotype.

Dataset Information

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

Publications

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

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