Pharmacogenetics in Cardiovascular Medicine

Tuteja, Sony; Limdi, Nita A.

doi:10.1007/s40142-016-0096-z

Cited by 11 publications

(7 citation statements)

References 90 publications

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“…For patients with combinations of high risk variants, an alternative anticoagulant might be considered. This is consistent with the United States Food and Drug Administration (FDA) which recently included recommendations for dosing table based on CYP2C9 and VKORC1 genotypes in its warfarin label update …”

Section: Cyp Genotype‐based Drug Therapiessupporting

confidence: 79%

“…Most guidelines published by professional or regulatory bodies (such as ACCF and FDA) do not yet recommend pharmacogenetic testings for CYP2C19 and clinicians are advised to consider the tests when warranted . Several ongoing RCTs will probably shed more lights on the clinical utility of a pharmacogenetic‐directed strategy, including potential economic benefits . Outcomes of these studies will inform its routine use in the near future.…”

Section: Cyp Genotype‐based Drug Therapiesmentioning

confidence: 99%

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Cytochrome P450 genotype‐guided drug therapies: An update on current states

Dong

Tan

Pan

et al. 2018

Clin Exp Pharma Physio

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Over the past 2 decades, knowledge of the role and clinical value of pharmacogenetic markers has expanded so that individualized pre-emptive therapy based on genetic background of patients could be within reach for clinical implementation. This is evidenced from the frequent updating of drug labels that incorporates pharmacogenetic information (where compelling data become available) by the regulatory agencies (such as the US FDA), and the periodical publication of guidelines of specific therapeutic recommendations based on the results of pharmacogenetic tests by the pharmacogenetics working groups or consortiums of professional bodies. Clinical relevance of the cytochrome P450 (CYP) polymorphism related to dose, effectiveness and/or toxicity of key drugs are presented in this review, including that of warfarin, clopidogrel, tricyclic antidepressants, and proton pump inhibitors. Prospect for routine clinical application of CYP genotyping before prescribing drugs is still currently unclear due to challenges and barriers associated with availability of well-defined and validated pharmacogenetic studies, the interpretation, result reporting and potential error of genotype testing, involvement of non-genetic factors, and other patient's demographic and disease conditions. Further studies to provide additional supporting clinical data and acceleration of pharmacogenetic testing standards and techniques should help improve the evidence base needed for clinical utility and hence move the implementation of genotype-guided therapy in clinical practice a step closer to reality.

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Section: Cyp Genotype‐based Drug Therapiessupporting

confidence: 79%

Section: Cyp Genotype‐based Drug Therapiesmentioning

confidence: 99%

Cytochrome P450 genotype‐guided drug therapies: An update on current states

Dong

Tan

Pan

et al. 2018

Clin Exp Pharma Physio

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“…Warfarin doses are usually established empirically and are adjusted by dose titration in line with the international normalized ratio (INR) for monitoring patients’ anticoagulant response. 2 , 6 , 7 Chemically, warfarin is a racemic mixture of R- and S-enantiomers acting on the coagulation cascade by inhibiting VKORC1, which prevents clotting factor carboxylation. The S-enantiomer is metabolized by the CYP2C9 enzyme.…”

Section: Introductionmentioning

confidence: 99%

“… 8 Genetic factors such as CYP2C9 and VKORC1 gene polymorphisms (eg, CYP2C9 *2, rs1799853; CYP2C9 *3, rs1057910; VKORC1 rs9923231) have been related to warfarin metabolism and dosage. 2 , 3 , 6 , 9 – 12 …”

Section: Introductionmentioning

confidence: 99%

Creating and validating a warfarin pharmacogenetic dosing algorithm for Colombian patients

Gálvez¹,

Restrepo²,

Contreras³

et al. 2018

PGPM

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PurposeWarfarin is an oral anticoagulant associated with adverse reaction to drugs due to wide inter- and intra-individual dosage variability. Warfarin dosage has been related to non-genetic and genetic factors. CYP2C9 and VKORC1 gene polymorphisms affect warfarin metabolism and dosage. Due to the central role of populations’ ethnical and genetic origin on warfarin dosage variability, novel algorithms for Latin American subgroups are necessary to establish safe anticoagulation therapy.Patients and methodsWe genotyped CYP2C9*2 (c.430C > T), CYP2C9*3 (c.1075A > C), CYP4F2 (c.1297G > A), and VKORC1 (−1639 G > A) polymorphisms in 152 Colombian patients who received warfarin. We evaluated the impact on the variability of patients’ warfarin dose requirements. Multiple linear regression analysis, using genetic and non-genetic variables, was used for creating an algorithm for optimal warfarin maintenance dose.ResultsMedian weekly prescribed warfarin dosage was significantly lower in patients having the VKORC1-1639 AA genotype and poor CYP2C9*2/*2,*2/*3 metabolizers than their wild-type counterparts. We found a 2.3-fold increase in mean dose for normal sensitivity patients (wild-type VKORC1/CYP2C9 genotypes) compared to the other groups (moderate and high sensitivity); 31.5% of the patients in our study group had warfarin sensitivity-related genotypes. The estimated regression equation accounted for 44.4% of overall variability in regard to warfarin maintenance dose. The algorithm was validated, giving 45.9% correlation (R2=0.459).ConclusionOur results describe and validate the first algorithm for predicting warfarin maintenance in a Colombian mestizo population and have contributed toward the understanding of pharmacogenetics in a Latin American population subgroup.

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“…При этом большинство фармакогенетических маркеров преодолевают барьер клинической валидности, и лишь немногие -клинической полезности. С этих позиций наиболее клинически валидными и клинически полезными для кардиологической практики являются пары ген -препарат: CYP2C19клопидогрел, CYP2C9 и VKORC1 -варфарин, и SLCO1B1 -статины [77]. ФГТ по данным маркерам уже внедрено в стандарты оказания медицинской помощи в Университете Флориды, где тестирование на полиморфизм гена CYP2C19 выполняется всем пациентам, перенесшим процедуру катетеризации сердца с 2012 г., а также в Университете Вандербильта, где перед назначением статинов проводится тестирование на полиморфизм гена SLCO1B1 [78].…”

Section: перспективы использования фармакогенетического тестирования unclassified

Multi-Ethnic Analysis of Cardiac Pharmacogenetic Markers of Cytochrome P450 and Membrane Transporters Genes in the Russian Population

Мирзаев

Fedorinov

Ivashchenko

et al. 2019

Racionalʹnaâ farmakoterapiâ v kardiologii

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Aim. To summarize Russian studies using pharmacogenetic testing as applied to cardiology.Material and methods. The authors conducted an online search for articles in December 2018 using the following databases: PubMed, Google Scholar, eLIBRARY. The search was carried out by keywords: "Russia", "Russian", "cardiology" together with the terms associated with the polymorphic marker, including: «P450», «CYP2C19», «CYP2D6», «CYP2B1», «CYP2B6», «CYP2Е1», «CYP2C8», «CYP2C9», «CYP3A4», «CYP3A5», «CYP1A1», «CYP1A2», «CYP4F2», «CYP4F1», «ABCB1», «SLCO1B1», «VKORC1», «GGCX», «SULT1A1», «CULT1», «CES1», «gene», «genes», «pharmacogenetics», «pharmacogenomics», «ethnic group».Results. Generalization of information allowed to identify obscure genes that need to be investigated in pharmacogenetic studies. This information can be used for the development of dosing algorithms and the priority choice of drugs, considering the results of pharmacogenetic testing and planning future research.Conclusion. The results of the literature review indicate the importance of studying the most clinically valid and clinically useful pharmacogenetic markers (CYP2C19, CYP2C9, VKORC1, SLCO1B1) among various ethnic groups in the Russian Federation. With the accumulation of evidence of clinical validity and clinical utility of other pharmacogenetic markers (CES1, CYP2D6*4, etc.), the problem of interethnic differences in the carriage of clinically significant polymorphisms of these genes identified in previous studies in the Russian Federation increasingly requires attention. The most promising for the introduction into the clinical practice in the Russian Federation in the near future are polymorphic markers of the CYP2C19, CYP2C9, VKORC1 and SLCO1B1 genes.

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Pharmacogenetics in Cardiovascular Medicine

Cited by 11 publications

References 90 publications

Cytochrome P450 genotype‐guided drug therapies: An update on current states

Cytochrome P450 genotype‐guided drug therapies: An update on current states

Creating and validating a warfarin pharmacogenetic dosing algorithm for Colombian patients

Multi-Ethnic Analysis of Cardiac Pharmacogenetic Markers of Cytochrome P450 and Membrane Transporters Genes in the Russian Population

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