Pharmacogenetics to Avoid Adverse Drug Reactions

A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Pharmacogenetics".

Deadline for manuscript submissions: closed (1 July 2021) | Viewed by 37729

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Special Issue Editor

Hospital Pharmacy and Pharmacogenomics, Instituto de Investigación Sanitaria Gregorio Marañón, Servicio de Farmacia, Hospital General Universitario Gregorio Marañón, Madrid, Spain
Interests: mRNA; Microarray; Gene Expression; Genomics; Molecular Biology; Cancer Research; Genetics; Gene Expression and Chromatin Biology; Transcription; PCR
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Special Issue Information

Dear colleagues,

Although a cure is the main goal of a treatment, serious adverse reactions associated with these treatments are a major problem in clinical practice and cost a lot of money for health systems. These adverse reactions limit the success of medicines and can even lead to the death of patients. Identifying the DNA variants associated with adverse drug reactions can help to personalize medicine and sustain health systems. This Special Issue focuses on these topics: the identification of DNA variants associated with adverse drug reactions, clinical application, and cost-effectiveness studies.

Dr. Luis A. López-Fernández
Guest Editor

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Keywords

  • pharmacogenetics
  • adverse drug reactions
  • the health system
  • clinical implementation

Published Papers (12 papers)

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Editorial

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3 pages, 199 KiB  
Editorial
Pharmacogenetics to Avoid Adverse Drug Reactions
by Luis A. López-Fernández
J. Pers. Med. 2022, 12(2), 159; https://doi.org/10.3390/jpm12020159 - 26 Jan 2022
Viewed by 2134
Abstract
Although a cure is the main goal of a treatment, serious adverse reactions associated with these treatments are a major problem in clinical practice and cost a lot of money for health systems [...] Full article
(This article belongs to the Special Issue Pharmacogenetics to Avoid Adverse Drug Reactions)

Research

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16 pages, 2242 KiB  
Article
Association of HLA-B*51:01, HLA-B*55:01, CYP2C9*3, and Phenytoin-Induced Cutaneous Adverse Drug Reactions in the South Indian Tamil Population
by Shobana John, Karuppiah Balakrishnan, Chonlaphat Sukasem, Tharmarajan Chinnathambi Vijay Anand, Bhutorn Canyuk and Sutthiporn Pattharachayakul
J. Pers. Med. 2021, 11(8), 737; https://doi.org/10.3390/jpm11080737 - 28 Jul 2021
Cited by 7 | Viewed by 2460
Abstract
Phenytoin (PHT) is one of the most commonly reported aromatic anti-epileptic drugs (AEDs) to cause cutaneous adverse reactions (CADRs), particularly severe cutaneous adverse reactions (SCARs). Although human leukocyte antigen (HLA)-B*15:02 is associated with PHT-induced Steven Johnson syndrome/toxic epidermal necrosis (SJS/TEN) in East Asians, [...] Read more.
Phenytoin (PHT) is one of the most commonly reported aromatic anti-epileptic drugs (AEDs) to cause cutaneous adverse reactions (CADRs), particularly severe cutaneous adverse reactions (SCARs). Although human leukocyte antigen (HLA)-B*15:02 is associated with PHT-induced Steven Johnson syndrome/toxic epidermal necrosis (SJS/TEN) in East Asians, the association is much weaker than it is reported for carbamazepine (CBZ). In this study, we investigated the association of pharmacogenetic variants of the HLA B gene and CYP2C9*3 with PHT-CADRs in South Indian epileptic patients. This prospective case-controlled study included 25 PHT-induced CADRs, 30 phenytoin-tolerant patients, and 463 (HLA-B) and 82 (CYP2C9*3) normal-controls from previous studies included for the case and normal-control comparison. Six SCARs cases and 19 mild-moderate reactions were observed among the 25 cases. Pooled data analysis was performed for the HLA B*51:01 and PHT-CADRs associations. The Fisher exact test and multivariate binary logistic regression analysis were used to identify the susceptible alleles associated with PHT-CADRs. Multivariate analysis showed that CYP2C9*3 was significantly associated with overall PHT-CADRs (OR = 12.00, 95% CI 2.759–84.87, p = 003). In subgroup analysis, CYP2C9*3 and HLA B*55:01 were found to be associated with PHT-SCARs (OR = 12.45, 95% CI 1.138–136.2, p = 0.003) and PHT-maculopapular exanthema (MPE) (OR = 4.041, 95% CI 1.125–15.67, p = 0.035), respectively. Pooled data analysis has confirmed the association between HLA B*51:01/PHT-SCARs (OR = 6.273, 95% CI 2.24–16.69, p = <0.001) and HLA B*51:01/PHT-overall CADRs (OR = 2.323, 95% CI 1.22–5.899, p = 0.037). In this study, neither the case nor the control groups had any patients with HLA B*15:02. The risk variables for PHT-SCARs, PHT-overall CADRs, and PHT-MPE were found to be HLA B*51:01, CYP2C9*3, and HLA B*55:01, respectively. These alleles were identified as the risk factors for the first time in the South Indian Tamil population for PHT-CADRs. Further investigation is warranted to establish the clinical relevance of these alleles in this population with larger sample size. Full article
(This article belongs to the Special Issue Pharmacogenetics to Avoid Adverse Drug Reactions)
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15 pages, 937 KiB  
Article
A Pharmacogenetic Study of CYP2C19 in Acute Coronary Syndrome Patients of Colombian Origin Reveals New Polymorphisms Potentially Related to Clopidogrel Therapy
by Mariana Angulo-Aguado, Karen Panche, Caroll Andrea Tamayo-Agudelo, Daniel-Armando Ruiz-Torres, Santiago Sambracos-Parrado, Maria Jose Niño-Orrego, Nathaly Páez, Laura B Piñeros-Hernandez, Luisa-Fernanda Castillo-León, Juan Mauricio Pardo-Oviedo, Katherine Parra Abaunza, Paul Laissue, Nora Contreras, Carlos Alberto Calderón-Ospina and Dora Janeth Fonseca-Mendoza
J. Pers. Med. 2021, 11(5), 400; https://doi.org/10.3390/jpm11050400 - 12 May 2021
Cited by 5 | Viewed by 2946
Abstract
Clopidogrel, an oral platelet P2Y12 receptor blocker, is used in the treatment of acute coronary syndrome. Interindividual variability in treatment response and the occurrence of adverse effects has been attributed to genetic variants in CYP2C19. The analysis of relevant pharmacogenes in [...] Read more.
Clopidogrel, an oral platelet P2Y12 receptor blocker, is used in the treatment of acute coronary syndrome. Interindividual variability in treatment response and the occurrence of adverse effects has been attributed to genetic variants in CYP2C19. The analysis of relevant pharmacogenes in ethnically heterogeneous and poorly studied populations contributes to the implementation of personalized medicine. We analyzed the coding and regulatory regions of CYP2C19 in 166 patients with acute coronary syndrome (ACS) treated with clopidogrel. The allele frequencies of CYP2C19 alleles *1, *2, *4, *17, *27 and *33 alleles were 86.1%, 7.2%, 0.3%, 10.2%, 0.3% and 0.3%, respectively. A new potentially pathogenic mutation (p.L15H) and five intronic variants with potential splicing effects were detected. In 14.4% of the patients, a new haplotype in strong linkage disequilibrium was identified. The clinical outcome indicated that 13.5% of the patients presented adverse drugs reactions with a predominance of bleeding while 25% of these patients were carriers of at least one polymorphic allele. We propose that new regulatory single-nucleotide variants (SNVs) might potentially influence the response to clopidogrel in Colombian individuals. Full article
(This article belongs to the Special Issue Pharmacogenetics to Avoid Adverse Drug Reactions)
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15 pages, 597 KiB  
Article
SLCO1B1 Phenotype and CYP3A5 Polymorphism Significantly Affect Atorvastatin Bioavailability
by Pablo Zubiaur, Maria Dolores Benedicto, Gonzalo Villapalos-García, Marcos Navares-Gómez, Gina Mejía-Abril, Manuel Román, Samuel Martín-Vílchez, Dolores Ochoa and Francisco Abad-Santos
J. Pers. Med. 2021, 11(3), 204; https://doi.org/10.3390/jpm11030204 - 13 Mar 2021
Cited by 19 | Viewed by 3496
Abstract
Atorvastatin, prescribed for the treatment of hypercholesterolemia, demonstrated overwhelming benefits in reducing cardiovascular morbidity and mortality. However, many patients discontinue therapy due to adverse reactions, especially myopathy. The Dutch Pharmacogenetics Working Group (DPWG) recommends an alternative agent to atorvastatin and simvastatin or a [...] Read more.
Atorvastatin, prescribed for the treatment of hypercholesterolemia, demonstrated overwhelming benefits in reducing cardiovascular morbidity and mortality. However, many patients discontinue therapy due to adverse reactions, especially myopathy. The Dutch Pharmacogenetics Working Group (DPWG) recommends an alternative agent to atorvastatin and simvastatin or a dose adjustment depending on other risk factors for statin-induced myopathy in SLCO1B1 rs4149056 CC or TC carriers. In contrast, the Clinical Pharmacogenetics Implementation Consortium (CPIC) published their guideline on simvastatin, but not on atorvastatin. In this work, we aimed to demonstrate the effect of SLCO1B1 phenotype and other variants (e.g., in CYP3A4/5, UGT enzymes or SLC transporters) on atorvastatin pharmacokinetics. For this purpose, a candidate-gene pharmacogenetic study was proposed. The study population comprised 156 healthy volunteers enrolled in atorvastatin bioequivalence clinical trials. The genotyping strategy comprised a total of 60 variants in 15 genes. Women showed higher exposure to atorvastatin compared to men (p = 0.001), however this difference disappeared after dose/weight (DW) correction. The most relevant pharmacogenetic differences were the following: AUC/DW and Cmax /DW based on (a) SLCO1B1 phenotype (p < 0.001 for both) and (b) CYP3A5*3 (p = 0.004 and 0.018, respectively). As secondary findings: SLC22A1 *2/*2 genotype was related to higher Cmax/DW (ANOVA p = 0.030) and SLC22A1 *1/*5 genotype was associated with higher Vd/F (ANOVA p = 0.032) compared to SLC22A1 *1/*1, respectively. Finally, UGT2B7 rs7439366 *1/*1 genotype was associated with higher tmax as compared with the *1/*3 genotype (ANOVA p = 0.024). Based on our results, we suggest that SLCO1B1 is the best predictor for atorvastatin pharmacokinetic variability and that prescription should be adjusted based on it. We suggest that the CPIC should include atorvastatin in their statin-SLCO1B1 guidelines. Interesting and novel results were observed based on CYP3A5 genotype, which should be confirmed with further studies. Full article
(This article belongs to the Special Issue Pharmacogenetics to Avoid Adverse Drug Reactions)
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16 pages, 1351 KiB  
Article
Application of a Pharmacogenetics-Based Precision Medicine Model (5SPM) to Psychotic Patients That Presented Poor Response to Neuroleptic Therapy
by Lorena Carrascal-Laso, Manuel Ángel Franco-Martín, María Belén García-Berrocal, Elena Marcos-Vadillo, Santiago Sánchez-Iglesias, Carolina Lorenzo, Almudena Sánchez-Martín, Ignacio Ramos-Gallego, M Jesús García-Salgado and María Isidoro-García
J. Pers. Med. 2020, 10(4), 289; https://doi.org/10.3390/jpm10040289 - 18 Dec 2020
Cited by 4 | Viewed by 2364
Abstract
Antipsychotics are the keystone of the treatment of severe and prolonged mental disorders. However, there are many risks associated with these drugs and not all patients undergo full therapeutic profit from them. The application of the 5 Step Precision Medicine model(5SPM), based on [...] Read more.
Antipsychotics are the keystone of the treatment of severe and prolonged mental disorders. However, there are many risks associated with these drugs and not all patients undergo full therapeutic profit from them. The application of the 5 Step Precision Medicine model(5SPM), based on the analysis of the pharmacogenetic profile of each patient, could be a helpful tool to solve many of the problematics traditionally associated with the neuroleptic treatment. In order to solve this question, a cohort of psychotic patients that showed poor clinical evolution was analyzed. After evaluating the relationship between the prescribed treatment and pharmacogenetic profile of each patient, a great number of pharmacological interactions and pharmacogenetical conflicts were found. After reconsidering the treatment of the conflictive cases, patients showed a substantial reduction on mean daily doses and polytherapy cases, which may cause less risk of adverse effects, greater adherence, and a reduction on economic costs. Full article
(This article belongs to the Special Issue Pharmacogenetics to Avoid Adverse Drug Reactions)
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20 pages, 562 KiB  
Article
Impact of Drug-Gene-Interaction, Drug-Drug-Interaction, and Drug-Drug-Gene-Interaction on (es)Citalopram Therapy: The PharmLines Initiative
by Muh. Akbar Bahar, Pauline Lanting, Jens H. J. Bos, Rolf H. Sijmons, Eelko Hak and Bob Wilffert
J. Pers. Med. 2020, 10(4), 256; https://doi.org/10.3390/jpm10040256 - 28 Nov 2020
Cited by 11 | Viewed by 3051
Abstract
We explored the association between CYP2C19/3A4 mediated drug-gene-interaction (DGI), drug-drug-interaction (DDI) and drug-drug-gene-interaction (DDGI) and (es)citalopram dispensing course. A cohort study was conducted among adult Caucasians from the Lifelines cohort (167,729 participants) and linked dispensing data from the IADB.nl database as part of [...] Read more.
We explored the association between CYP2C19/3A4 mediated drug-gene-interaction (DGI), drug-drug-interaction (DDI) and drug-drug-gene-interaction (DDGI) and (es)citalopram dispensing course. A cohort study was conducted among adult Caucasians from the Lifelines cohort (167,729 participants) and linked dispensing data from the IADB.nl database as part of the PharmLines Initiative. Exposure groups were categorized into (es)citalopram starters with DGI, DDI and DDGI. The primary outcome was drug switching and/or dose adjustment, and the secondary was early discontinuation after the start of (es)citalopram. Logistic regression modeling was applied to estimate adjusted odd ratios with their confidence interval. We identified 316 (es)citalopram starters with complete CYP2C19/3A4 genetic information. The CYP2C19 IM/PM and CYP3A4 NM combination increased risks of switching and/or dose reduction (OR: 2.75, 95% CI: 1.03–7.29). The higher effect size was achieved by the CYP2C19 IM/PM and CYP3A4 IM combination (OR: 4.38, 95% CI: 1.22–15.69). CYP2C19/3A4 mediated DDIs and DDGIs showed trends towards increased risks of switching and/or dose reduction. In conclusion, a DGI involving predicted decreased CYP2C19 function increases the need for (es)citalopram switching and/or dose reduction which might be enhanced by co-presence of predicted decreased CYP3A4 function. For DDI and DDGI, no conclusions can be drawn from the results. Full article
(This article belongs to the Special Issue Pharmacogenetics to Avoid Adverse Drug Reactions)
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14 pages, 1158 KiB  
Article
Genome Wide Epistasis Study of On-Statin Cardiovascular Events with Iterative Feature Reduction and Selection
by Solomon M. Adams, Habiba Feroze, Tara Nguyen, Seenae Eum, Cyrille Cornelio and Arthur F. Harralson
J. Pers. Med. 2020, 10(4), 212; https://doi.org/10.3390/jpm10040212 - 07 Nov 2020
Cited by 6 | Viewed by 2350
Abstract
Predicting risk for major adverse cardiovascular events (MACE) is an evidence-based practice that incorporates lifestyle, history, and other risk factors. Statins reduce risk for MACE by decreasing lipids, but it is difficult to stratify risk following initiation of a statin. Genetic risk determinants [...] Read more.
Predicting risk for major adverse cardiovascular events (MACE) is an evidence-based practice that incorporates lifestyle, history, and other risk factors. Statins reduce risk for MACE by decreasing lipids, but it is difficult to stratify risk following initiation of a statin. Genetic risk determinants for on-statin MACE are low-effect size and impossible to generalize. Our objective was to determine high-level epistatic risk factors for on-statin MACE with GWAS-scale data. Controlled-access data for 5890 subjects taking a statin collected from Vanderbilt University Medical Center’s BioVU were obtained from dbGaP. We used Random Forest Iterative Feature Reduction and Selection (RF-IFRS) to select highly informative genetic and environmental features from a GWAS-scale dataset of patients taking statin medications. Variant-pairs were distilled into overlapping networks and assembled into individual decision trees to provide an interpretable set of variants and associated risk. 1718 cases who suffered MACE and 4172 controls were obtained from dbGaP. Pathway analysis showed that variants in genes related to vasculogenesis (FDR = 0.024), angiogenesis (FDR = 0.019), and carotid artery disease (FDR = 0.034) were related to risk for on-statin MACE. We identified six gene-variant networks that predicted odds of on-statin MACE. The most elevated risk was found in a small subset of patients carrying variants in COL4A2, TMEM178B, SZT2, and TBXAS1 (OR = 4.53, p < 0.001). The RF-IFRS method is a viable method for interpreting complex “black-box” findings from machine-learning. In this study, it identified epistatic networks that could be applied to risk estimation for on-statin MACE. Further study will seek to replicate these findings in other populations. Full article
(This article belongs to the Special Issue Pharmacogenetics to Avoid Adverse Drug Reactions)
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13 pages, 831 KiB  
Article
A Novel Nomenclature for Repeat Motifs in the Thymidylate Synthase Enhancer Region and Its Relevance for Pharmacogenetic Studies
by Dominic Schaerer, Tanja K. Froehlich, Seid Hamzic, Steven M. Offer, Robert B. Diasio, Markus Joerger, Ursula Amstutz and Carlo R. Largiadèr
J. Pers. Med. 2020, 10(4), 181; https://doi.org/10.3390/jpm10040181 - 19 Oct 2020
Cited by 6 | Viewed by 1939
Abstract
Inhibition of thymidylate synthase (TS) is the primary mode of action for 5-fluorouracil (5FU) chemotherapy. TS expression is modulated by a variable number of tandem repeats in the TS enhancer region (TSER) located upstream of the TS gene (TYMS). Variability in [...] Read more.
Inhibition of thymidylate synthase (TS) is the primary mode of action for 5-fluorouracil (5FU) chemotherapy. TS expression is modulated by a variable number of tandem repeats in the TS enhancer region (TSER) located upstream of the TS gene (TYMS). Variability in the TSER has been suggested to contribute to 5FU-induced adverse events. However, the precise genetic associations remain largely undefined due to high polymorphism and ambiguity in defining genotypes. To assess toxicity associations, we sequenced the TSER in 629 cancer patients treated with 5FU. Of the 13 alleles identified, few could be unambiguously named using current TSER-nomenclature. We devised a concise and unambiguous systematic naming approach for TSER-alleles that encompasses all known variants. After applying this comprehensive naming system to our data, we demonstrated that the number of upstream stimulatory factor (USF1-)binding sites in the TSER was significantly associated with gastrointestinal toxicity in 5FU treatment. Full article
(This article belongs to the Special Issue Pharmacogenetics to Avoid Adverse Drug Reactions)
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Review

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19 pages, 335 KiB  
Review
Pharmacogenetics to Avoid Adverse Reactions in Cardiology: Ready for Implementation?
by Xandra García-González and Sara Salvador-Martín
J. Pers. Med. 2021, 11(11), 1180; https://doi.org/10.3390/jpm11111180 - 11 Nov 2021
Cited by 4 | Viewed by 2446
Abstract
Cardiovascular Diseases (CVs) are one of the main causes of mortality and disability around the world. Advances in drug treatment have greatly improved survival and quality of life in the past decades, but associated adverse events remain a relevant problem. Pharmacogenetics can help [...] Read more.
Cardiovascular Diseases (CVs) are one of the main causes of mortality and disability around the world. Advances in drug treatment have greatly improved survival and quality of life in the past decades, but associated adverse events remain a relevant problem. Pharmacogenetics can help individualize cardiovascular treatment, reducing associated toxicities and improving outcomes. Several scientific societies and working groups periodically review available studies and provide consensus recommendations for those gene-drug pairs with a sufficient level of evidence. However, these recommendations are rarely mandatory, and the indications on how to adjust treatment can vary between different guidelines, which limits their clinical applicability. The aim of this review is to compile, compare and discuss available guidelines and recommendations by the main Pharmacogenetics Consortiums (Clinical Pharmacogenetics Implementation Consortium (CPIC); Dutch Pharmacogenetics Working Group (DPWG); the French Network of Pharmacogenetics (Réseau national de pharmacogénétique (RNPGx) and The Canadian Pharmacogenomics Network for Drug Safety (CPNDS) regarding how to apply pharmacogenetic results to optimize pharmacotherapy in cardiology. Pharmacogenetic recommendations included in European or American drug labels, as well as those included in the European Society of Cardiology (ESC) and the American College of Cardiology (ACC) and the American Heart Association (AHA) treatment guidelines are also discussed. Full article
(This article belongs to the Special Issue Pharmacogenetics to Avoid Adverse Drug Reactions)
19 pages, 1471 KiB  
Review
Genetic Determinants in HLA and Cytochrome P450 Genes in the Risk of Aromatic Antiepileptic-Induced Severe Cutaneous Adverse Reactions
by Ali Fadhel Ahmed, Chonlaphat Sukasem, Majeed Arsheed Sabbah, Nur Fadhlina Musa, Dzul Azri Mohamed Noor and Nur Aizati Athirah Daud
J. Pers. Med. 2021, 11(5), 383; https://doi.org/10.3390/jpm11050383 - 07 May 2021
Cited by 6 | Viewed by 4162
Abstract
Adverse drug reaction (ADR) is a pressing health problem, and one of the main reasons for treatment failure with antiepileptic drugs. This has become apparent in the event of severe cutaneous adverse reactions (SCARs), which can be life-threatening. In this review, four hypotheses [...] Read more.
Adverse drug reaction (ADR) is a pressing health problem, and one of the main reasons for treatment failure with antiepileptic drugs. This has become apparent in the event of severe cutaneous adverse reactions (SCARs), which can be life-threatening. In this review, four hypotheses were identified to describe how the immune system is triggered in the development of SCARs, which predominantly involve the human leukocyte antigen (HLA) proteins. Several genetic variations in HLA genes have been shown to be strongly associated with the susceptibility to developing SCARs when prescribed carbamazepine or phenytoin. These genetic variations were also shown to be prevalent in certain populations. Apart from the HLA genes, other genes proposed to affect the risk of SCARs are genes encoding for CYP450 drug-metabolising enzymes, which are involved in the pharmacokinetics of offending drugs. Genetic variants in CYP2C9 and CYPC19 enzymes were also suggested to modulate the risk of SCARs in some populations. This review summarizes the literature on the manifestation and aetiology of antiepileptic-induced SCARs, updates on pharmacogenetic markers associated with this reaction and the implementation of pre-emptive testing as a preventive strategy for SCARs. Full article
(This article belongs to the Special Issue Pharmacogenetics to Avoid Adverse Drug Reactions)
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11 pages, 310 KiB  
Review
Pharmacogenetics of Direct Oral Anticoagulants: A Systematic Review
by Johanna Raymond, Laurent Imbert, Thibault Cousin, Thomas Duflot, Rémi Varin, Julien Wils and Fabien Lamoureux
J. Pers. Med. 2021, 11(1), 37; https://doi.org/10.3390/jpm11010037 - 11 Jan 2021
Cited by 55 | Viewed by 6440
Abstract
Dabigatran, rivaroxaban, apixaban, edoxaban, and betrixaban are direct oral anticoagulants (DOACs). Their inter-individual variability in pharmacodynamics and pharmacokinetics (transport and metabolism) is high, and could result from genetic polymorphisms. As recommended by the French Network of Pharmacogenetics (RNPGx), the management of some treatments [...] Read more.
Dabigatran, rivaroxaban, apixaban, edoxaban, and betrixaban are direct oral anticoagulants (DOACs). Their inter-individual variability in pharmacodynamics and pharmacokinetics (transport and metabolism) is high, and could result from genetic polymorphisms. As recommended by the French Network of Pharmacogenetics (RNPGx), the management of some treatments in cardiovascular diseases (as antiplatelet agents, oral vitamin K antagonists, and statins) can rely on genetic testing in order to improve healthcare by reducing therapeutic resistance or toxicity. This paper is a review of association studies between single nucleotide polymorphisms (SNPs) and systemic exposure variation of DOACs. Most of the results presented here have a lot to do with some SNPs of CES1 (rs2244613, rs8192935, and rs71647871) and ABCB1 (rs1128503, rs2032582, rs1045642, and rs4148738) genes, and dabigatran, rivaroxaban, and apixaban. Regarding edoxaban and betrixaban, as well as SNPs in the CYP3A4 and CYP3A5 genes, literature is scarce, and further studies are needed. Full article
(This article belongs to the Special Issue Pharmacogenetics to Avoid Adverse Drug Reactions)
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40 pages, 1437 KiB  
Review
The Road so Far in Colorectal Cancer Pharmacogenomics: Are We Closer to Individualised Treatment?
by Ana Rita Simões, Ceres Fernández-Rozadilla, Olalla Maroñas and Ángel Carracedo
J. Pers. Med. 2020, 10(4), 237; https://doi.org/10.3390/jpm10040237 - 19 Nov 2020
Cited by 4 | Viewed by 2778
Abstract
In recent decades, survival rates in colorectal cancer have improved greatly due to pharmacological treatment. However, many patients end up developing adverse drug reactions that can be severe or even life threatening, and that affect their quality of life. These remain a limitation, [...] Read more.
In recent decades, survival rates in colorectal cancer have improved greatly due to pharmacological treatment. However, many patients end up developing adverse drug reactions that can be severe or even life threatening, and that affect their quality of life. These remain a limitation, as they may force dose reduction or treatment discontinuation, diminishing treatment efficacy. From candidate gene approaches to genome-wide analysis, pharmacogenomic knowledge has advanced greatly, yet there is still huge and unexploited potential in the use of novel technologies such as next-generation sequencing strategies. This review summarises the road of colorectal cancer pharmacogenomics so far, presents considerations and directions to be taken for further works and discusses the path towards implementation into clinical practice. Full article
(This article belongs to the Special Issue Pharmacogenetics to Avoid Adverse Drug Reactions)
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