Pharmacogenetic Landscape of Clopidogrel in North Indians Suggest Distinct Interpopulation Differences in Allele Frequencies

Giri, Anil; Khan, Nazir M.; Basu, Analabha; Tandon, Nikhil; Scaria, Vinod; Bharadwaj, Dwaipayan

doi:10.2217/pgs.13.241

Cited by 18 publications

(10 citation statements)

References 29 publications

(22 reference statements)

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“…To the best of our knowledge creation of such a genotype frequency map at the population scale level to guide initial warfarin dosing in clinical practice has not been used before, hence, the value of this approach in improving the outcomes cannot been established at present. Nonetheless, a recent study used a similar approach to create a pharmacogenetic landscape to guide appropriate dosage for the antiplatelet drug clopidogrel among north Indians [40]. This kind of genetic epidemiological analysis provides a platform to predict the drug response and helps in minimizing the associated risk.…”

Section: Discussionmentioning

confidence: 99%

Genetic Epidemiology of Pharmacogenetic Variations in CYP2C9 , CYP4F2 and VKORC1 Genes Associated with Warfarin Dosage in the Indian Population

et al. 2014

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Based on genotypic distribution, the majority of the Indian subpopulation might require higher doses for stable anticoagulation, whereas careful assessment is required for Tibeto-Burmans who are expected to have intermediate dose requirement. This is the largest global genetic epidemiological study examining variants associated with warfarin that could potentially be valuable to clinicians in optimizing dosage strategies.

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Section: Discussionmentioning

confidence: 99%

Genetic Epidemiology of Pharmacogenetic Variations in CYP2C9 , CYP4F2 and VKORC1 Genes Associated with Warfarin Dosage in the Indian Population

et al. 2014

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“…One study identified lower frequency of the CYP2C19*2 variant in North Indians of Asian descent compared with the global population [ 136 ], while another study suggested comparable frequencies (40–47%) in Asian Indian patients with ischemic heart disease [ 137 ]. A meta-analysis showed that carrier status for LOF genetic variants in CYP2C19 associated with increased risk of adverse clinical events [ 138 ].…”

Section: Regulators Of Responsementioning

confidence: 99%

Pharmacogenomic Impact of CYP2C19 Variation on Clopidogrel Therapy in Precision Cardiovascular Medicine

Brown

Pereira

2018

JPM

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Variability in response to antiplatelet therapy can be explained in part by pharmacogenomics, particularly of the CYP450 enzyme encoded by CYP2C19. Loss-of-function and gain-of-function variants help explain these interindividual differences. Individuals may carry multiple variants, with linkage disequilibrium noted among some alleles. In the current pharmacogenomics era, genomic variation in CYP2C19 has led to the definition of pharmacokinetic phenotypes for response to antiplatelet therapy, in particular, clopidogrel. Individuals may be classified as poor, intermediate, extensive, or ultrarapid metabolizers, based on whether they carry wild type or polymorphic CYP2C19 alleles. Variant alleles differentially impact platelet reactivity, concentration of plasma clopidogrel metabolites, and clinical outcomes. Interestingly, response to clopidogrel appears to be modulated by additional factors, such as sociodemographic characteristics, risk factors for ischemic heart disease, and drug-drug interactions. Furthermore, systems medicine studies suggest that a broader approach may be required to adequately assess, predict, preempt, and manage variation in antiplatelet response. Transcriptomics, epigenomics, exposomics, miRNAomics, proteomics, metabolomics, microbiomics, and mathematical, computational, and molecular modeling should be integrated with pharmacogenomics for enhanced prediction and individualized care. In this review of pharmacogenomic variation of CYP450, a systems medicine approach is described for tailoring antiplatelet therapy in clinical practice of precision cardiovascular medicine.

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“…Prevalence of PGx variations have been demonstrated to vary substantially between populations. [65] Depending on the testing platform used, rare variants may be missed [66], including those present in less studied populations, thereby limiting benefit of testing to some population groups due to the prevalence disparities between groups. [67] For minority patients, use of PGx gene panels may return more uncertain findings [68] and providers should disclose this to patients and be prepared for this possibility when discussing test results.…”

Section: Barriers To Test Utilizationmentioning

confidence: 99%

Integrating pharmacogenetic testing into primary care

Haga

2017

Expert Review of Precision Medicine and Drug Development

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Introduction Pharmacogenetic (PGx) testing has greatly expanded due to enhanced understanding of the role of genes in drug response and advances in DNA-based testing technology development. As many primary care visits result in a prescription, the use of PGx testing may be particularly beneficial in this setting. However, integration of PGx testing may be limited as no uniform approach to delivery of tests has been established and providers are ill-prepared to integrate PGx testing into routine care. Areas covered In this paper, the readiness of primary care practitioners are reviewed as well as strategies to address these barriers based on published research and ongoing activities on education and implementation of PGx testing. Expert Commentary Widespread integration of PGx testing will warrant continued education and point-of-care decisional support. Primary care providers may also benefit from consultation services or team-based care with laboratory medicine specialists, pharmacists, and genetic counselors.

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Pharmacogenetic Landscape of Clopidogrel in North Indians Suggest Distinct Interpopulation Differences in Allele Frequencies

Cited by 18 publications

References 29 publications

Genetic Epidemiology of Pharmacogenetic Variations in CYP2C9 , CYP4F2 and VKORC1 Genes Associated with Warfarin Dosage in the Indian Population

Genetic Epidemiology of Pharmacogenetic Variations in CYP2C9 , CYP4F2 and VKORC1 Genes Associated with Warfarin Dosage in the Indian Population

Pharmacogenomic Impact of CYP2C19 Variation on Clopidogrel Therapy in Precision Cardiovascular Medicine

Integrating pharmacogenetic testing into primary care

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