Clinical Pharmacogenetics Implementation Consortium Guidelines for HLA-B Genotype and Abacavir Dosing

Martin, Michael A.; Klein, Teri E.; Dong, Betty J.; Pirmohamed, Munir; Haas, David W.; Kroetz, Deanna L.

doi:10.1038/clpt.2011.355

Cited by 178 publications

(166 citation statements)

References 39 publications

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“…variantes de CYP2C9 y farmacocinética de warfarina y acenocumarol), en comparación con las investigaciones de genes candidatos de susceptibilidad a una enfermedad en particular. Esto se debe posiblemente a que existe una mayor comprensión de las vías metabólicas de un fármaco, en comparación con complejos procesos que influyen en el desarrollo de una enfermedad 21,23 .…”

Section: Aplicaciones De La Farmacogenómica En La Clínicaunclassified

Farmacogenómica como herramienta fundamental para la medicina personalizada: aplicaciones en la práctica clínica

et al. 2017

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Pharmacogenomics is an emergent field aimed at tailoring pharmacological therapy. Genetic polymorphisms can modify the expression and function of enzymes and proteins involved in drug metabolism, affecting absorption, distribution, biotransformation and excretion as well asU n hecho bien conocido es que los pacientes responden en forma diferente frente a la farmacoterapia y que ningún medicamento es 100% eficaz en todos los pacientes. Esta respuesta variable se debe, en gran medida, a factores genéticos, epigenéticos y ambientales, que afectan a las proteínas que metabolizan o transportan los fármacos, sus blancos terapéuticos (receptores) o ambos, influenciando tanto su eficacia como su seguridad, y en donde la contribución de cada factor varía en cada fármaco 1-4 . La Tabla 1 resume los factores que condicionan la variación interindividual en la respuesta a fármacos.Debido al desarrollo de técnicas no invasivas de ingeniería genética y biología molecular y a la necesidad de encontrar una explicación a las variaciones en la respuesta a la acción de fármacos es que actualmente la farmacogenómica ha adquirido gran relevancia en la investigación farmacológica. Es así como los resultados de los del Proyectos Genoma Humano 7 , Internacional HapMap 8 1.000 Genomas, el consorcio SNP 9 y los estudios GWAS (Genome-Wide Association Studies) 10 han aportado importantemente a nuestra comprensión de la variación genética humana 5,11,12 . Actualmente se sabe que existen 20.296 genes codificantes, 148.892.479 SNPs (polimorfismos de un solo nucleótido) y 4.363.564 variantes estructurales

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Section: Aplicaciones De La Farmacogenómica En La Clínicaunclassified

Farmacogenómica como herramienta fundamental para la medicina personalizada: aplicaciones en la práctica clínica

et al. 2017

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“…Specifically, carriers of this variant are thought to have up to a 117-fold increased risk of developing abacavir HSR [71,73]. Epidemiologically, the HLA-B*5701 frequency in Europeans ranges from 1.4-10.3%, and in Asians from 3.8-19.8%; additionally, it ranges 1.1-3.1% in South Americans [74,75]. Consequently, the Infectious Disease Society of America has recommended HLA-B*5701 genotyping prior to starting ISSN: 2474ISSN: -1914 patients on abacavir [72,76].…”

Section: Immune-mediated Responsesmentioning

confidence: 99%

Application and Utility of Pharmacogenetics in the Clinical Laboratory

2014

J Analyt Molecul Tech

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The administration of pharmaceuticals presents a challenge for the healthcare system, as inappropriate drug or dose selection can result in diminished therapeutic efficacy or adverse drug reactions. Genetic variability is a major regulator of drug action and should be taken into account during drug and dose selection. The correlation of drug responses (phenotypes) to specific polymorphisms (genotype) has contributed to the development of many targeted genotyping approaches. Incorporation of such testing into the clinical laboratory requires the evaluation of current testing platform characteristics as well as the selection of appropriate polymorphisms to be tested. Here we describe known genotype -phenotype relationships pertinent to drug action and present currently available targeted genotyping platforms for pharmacogenetics (PGx) testing. We additionally discuss considerations regarding platform and polymorphism selection for successful integration of PGx testing into the clinical laboratory and attainment of clinically useful results.

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“…Given these limitations as well as the lack of cost-effectiveness data, it is not surprising that the SSRIs are not good candidates for genotype-based pharmacogenomic therapy and, hence, the recommendation of the EGAPP Working Group. Other pharmacogenomic biomarkers could be better candidates for testing association between specific genotype and clinical phenotype [55][56][57][58][59][60][61][62][63], as indicated by published guidelines. Pharmacogenetic dosing algorithms [37,39] based on the patient's CYP2C9 and VKORC1 genotypes and other nongenetic factors (e.g., age, body size, and concurrent interacting drug) have been used to determine warfarin dosage regimens.…”

Section: Analyticalmentioning

confidence: 99%

Scientific Challenges and Implementation Barriers to Translation of Pharmacogenomics in Clinical Practice

Lam¹

2014

Omics in Clinical Practice

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The mapping of the human genome and subsequent advancements in genetic technology had provided clinicians and scientists an understanding of the genetic basis of altered drug pharmacokinetics and pharmacodynamics, as well as some examples of applying genomic data in clinical practice. This has raised the public expectation that predicting patients' responses to drug therapy is now possible in every therapeutic area, and personalized drug therapy would come sooner than later. However, debate continues among most stakeholders involved in drug development and clinical decision-making on whether pharmacogenomic biomarkers should be used in patient assessment, as well as when and in whom to use the biomarker-based diagnostic tests. Currently, most would agree that achieving the goal of personalized therapy remains years, if not decades, away. Realistic application of genomic findings and technologies in clinical practice and drug development require addressing multiple logistics and challenges that go beyond discovery of gene variants and/or completion of prospective controlled clinical trials. The goal of personalized medicine can only be achieved when all stakeholders in the field work together, with willingness to accept occasional paradigm change in their current approach.

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Clinical Pharmacogenetics Implementation Consortium Guidelines for HLA-B Genotype and Abacavir Dosing

Cited by 178 publications

References 39 publications

Farmacogenómica como herramienta fundamental para la medicina personalizada: aplicaciones en la práctica clínica

Farmacogenómica como herramienta fundamental para la medicina personalizada: aplicaciones en la práctica clínica

Application and Utility of Pharmacogenetics in the Clinical Laboratory

Scientific Challenges and Implementation Barriers to Translation of Pharmacogenomics in Clinical Practice

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