-
Journal of Clinical PsychopharmacologyThe purpose of this study was to review the association between the SLC6A4 5-HTTLPR polymorphism and antidepressant (AD)-associated treatment emergent mania (TEM) in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The purpose of this study was to review the association between the SLC6A4 5-HTTLPR polymorphism and antidepressant (AD)-associated treatment emergent mania (TEM) in bipolar disorder alongside starting a discussion on the merits of developing risk stratification models to guide when not to provide AD treatment for bipolar depression.
METHODS
Studies that examined the association between clinical and genetic risk factors, specifically monoaminergic transporter genetic variation, and TEM were identified. A meta-analysis was performed using the odds ratio to estimate the effect size under the Der-Simonian and Laird model.
RESULTS
Seven studies, referencing the SLC6A4 5-HTTLPR polymorphism and TEM (total N = 1578; TEM+ =594, TEM- = 984), of 142 identified articles were included. The time duration between the start of the AD to emergence of TEM ranged from 4 to 12 weeks. There was a nominally significant association between the s allele of the 5-HTTLPR polymorphism and TEM (odds ratio, 1.434; 95% confidence interval, 1.001-2.055; P = 0.0493; I2 = 52%). No studies have investigated norepinephrine or dopamine transporters.
CONCLUSION
Although the serotonin transporter genetic variation is commercially available in pharmacogenomic decision support tools, greater efforts, more broadly, should focus on complete genome-wide approaches to determine genetic variants that may contribute to TEM. Moreover, these data are exemplary to the merits of developing risk stratification models, which include both clinical and biological risk factors, to guide when not to use ADs in bipolar disorder. Future studies will need to validate new risk models that best inform the development of personalized medicine best practices treating bipolar depression.
Topics: Humans; Antidepressive Agents; Bipolar Disorder; Mania; Pharmacogenetics; Polymorphism, Genetic; Serotonin Plasma Membrane Transport Proteins
PubMed: 37683232
DOI: 10.1097/JCP.0000000000001747 -
Genes Nov 2023Advances in pharmacogenomics have paved the way for personalized medicine. Cardiovascular diseases still represent the leading cause of mortality in the world. The aim... (Review)
Review
PURPOSE OF REVIEW
Advances in pharmacogenomics have paved the way for personalized medicine. Cardiovascular diseases still represent the leading cause of mortality in the world. The aim of this review is to summarize the background, rationale, and evidence of pharmacogenomics in cardiovascular medicine, in particular, the use of antiplatelet drugs, anticoagulants, and drugs used for the treatment of dyslipidemia.
RECENT FINDINGS
Randomized clinical trials have supported the role of a genotype-guided approach for antiplatelet therapy in patients with coronary heart disease undergoing percutaneous coronary interventions. Numerous studies demonstrate how the risk of ineffectiveness of new oral anticoagulants and vitamin K anticoagulants is linked to various genetic polymorphisms. Furthermore, there is growing evidence to support the association of some genetic variants and poor adherence to statin therapy, for example, due to the appearance of muscular symptoms. There is evidence for resistance to some drugs for the treatment of dyslipidemia, such as anti-PCSK9.
SUMMARY
Pharmacogenomics has the potential to improve patient care by providing the right drug to the right patient and could guide the identification of new drug therapies for cardiovascular disease. This is very important in cardiovascular diseases, which have high morbidity and mortality. The improvement in therapy could be reflected in the reduction of healthcare costs and patient mortality.
Topics: Humans; Pharmacogenetics; Cardiovascular Agents; Cardiovascular Diseases; Anticoagulants; Dyslipidemias
PubMed: 38003001
DOI: 10.3390/genes14112057 -
The Journal of Applied Laboratory... Jan 2024Pharmacogenetics or pharmacogenomics (PGx) is the study of the role of inherited or acquired sequence change in drug response. With the rapid evolution of molecular...
BACKGROUND
Pharmacogenetics or pharmacogenomics (PGx) is the study of the role of inherited or acquired sequence change in drug response. With the rapid evolution of molecular techniques, bioinformatic tools, and increased throughput of functional genomic studies, the discovery of PGx associations and clinical implementation of PGx test results have now moved beyond a handful variants in single pharmacogenes and multi-gene panels that interrogate a few pharmacogenes to whole-exome and whole-genome scales. Although some laboratories have adopted next-generation sequencing (NGS) as a testing platform for PGx and other molecular tests, most clinical laboratories that offer PGx tests still use targeted genotyping approaches.
CONTENT
This article discusses primarily the technical considerations for clinical laboratories to develop NGS-based PGx tests including whole-genome and whole-exome sequencing analyses and highlights the challenges and opportunities in test design, content selection, bioinformatic pipeline for PGx allele and diplotype assignment, rare variant classification, reporting, and briefly touches a few additional areas that are important for successful clinical implementation of PGx results.
SUMMARY
The accelerated speed of technology development associated with continuous cost reduction and enhanced ability to interrogate complex genome regions makes it inevitable for most, if not all, clinical laboratories to transition PGx testing to an NGS-based platform in the near future. It is important for laboratories and relevant professional societies to recognize both the potential and limitations of NGS-based PGx profiling, and to work together to develop a standard and consistent practice to maximize the variant or allele detection rate and utility of PGx testing.
Topics: Humans; Pharmacogenetics; Alleles; Computational Biology; High-Throughput Nucleotide Sequencing
PubMed: 38167765
DOI: 10.1093/jalm/jfad097 -
Journal of the American Association of... Apr 2024Guided by Clinical Pharmacogenomic Implementation Consortium (CPIC) guidelines for >140 medications, pharmacogenomic tests inform medication selection and dosing to...
BACKGROUND
Guided by Clinical Pharmacogenomic Implementation Consortium (CPIC) guidelines for >140 medications, pharmacogenomic tests inform medication selection and dosing to optimize efficacy while minimizing toxicities.
PURPOSE
This study assessed pharmacogenomic self-reported curricular content, knowledge, skills, attitudes, and usage in advanced practice registered nurses (APRNs) with prescriptive privileges.
METHODOLOGY
An online survey was administered assessing pharmacogenomic curricular content, knowledge, skills, attitudes, and usage.
RESULTS
Data from 266 APRNs were analyzed. Most graduated with their highest nursing degree ∼10 years ago and reported pharmacogenomic curricular content (n = 124, 48%). Pharmacogenomic curricular content was associated with pharmacogenomic familiarity (p = .045) but not with knowledge confidence (p = .615). Pharmacogenomic usage, defined as ordering a pharmacogenomic test within the past year, was low (n = 76, 29%) and most (n = 210, 84%) reported never using CPIC Guidelines. Advanced practice registered nurses (n = 162) who did not anticipate ordering a pharmacogenomic test in the next year (n = 77, 48%) indicated that they did not know what test to order.
CONCLUSIONS
Deficits were identified in APRN pharmacogenomic knowledge and skills despite academic training. Most reported not ordering pharmacogenomic tests, did not know what test to order, and did not use CPIC guidelines.
IMPLICATIONS
Pharmacogenomics is a quality and safety issue. Academic training did not result in practice integration and most reported capacity deficits. Recommendation for overcoming academic deficits include: (1) assessment of pharmacogenomics curricular content and faculty teaching capacity; (2) training addressing identified deficiencies; and (3) Commission of Collegiate Nursing Education policies that include pharmacogenomics in advanced pharmacology. Practicing APRN plans include on-the-job training and/or mandatory training at the time of relicensure.
PubMed: 38595133
DOI: 10.1097/JXX.0000000000001007 -
International Journal of Molecular... Apr 2024In this short review we have presented and discussed studies on pharmacogenomics (also termed pharmacogenetics) of the drugs employed in the treatment of β-thalassemia... (Review)
Review
In this short review we have presented and discussed studies on pharmacogenomics (also termed pharmacogenetics) of the drugs employed in the treatment of β-thalassemia or Sickle-cell disease (SCD). This field of investigation is relevant, since it is expected to help clinicians select the appropriate drug and the correct dosage for each patient. We first discussed the search for DNA polymorphisms associated with a high expression of γ-globin genes and identified this using GWAS studies and CRISPR-based gene editing approaches. We then presented validated DNA polymorphisms associated with a high HbF production (including, but not limited to the XmnI polymorphism and those related to the , , , and genes). The expression of microRNAs involved in the regulation of γ-globin genes was also presented in the context of pharmacomiRNomics. Then, the pharmacogenomics of validated fetal hemoglobin inducers (hydroxyurea, butyrate and butyrate analogues, thalidomide, and sirolimus), of iron chelators, and of analgesics in the pain management of SCD patients were considered. Finally, we discuss current clinical trials, as well as international research networks focusing on clinical issues related to pharmacogenomics in hematological diseases.
Topics: Humans; Anemia, Sickle Cell; beta-Thalassemia; Pharmacogenetics; Fetal Hemoglobin; gamma-Globins; Iron Chelating Agents
PubMed: 38673849
DOI: 10.3390/ijms25084263 -
Journal of Clinical Oncology : Official... Aug 2023
Topics: Humans; Pharmacogenomic Testing; Informed Consent; Pharmacogenetics; Genetic Testing
PubMed: 37267582
DOI: 10.1200/JCO.23.00664 -
British Journal of Clinical Pharmacology Nov 2023Adverse drug reactions (ADRs) account for a large proportion of hospitalizations among adults and are more common in multimorbid patients, worsening clinical outcomes... (Review)
Review
Adverse drug reactions (ADRs) account for a large proportion of hospitalizations among adults and are more common in multimorbid patients, worsening clinical outcomes and burdening healthcare resources. Over the past decade, pharmacogenomics has been developed as a practical tool for optimizing treatment outcomes by mitigating the risk of ADRs. Some single-gene reactive tests are already used in clinical practice, including the DPYD test for fluoropyrimidines, which demonstrates how integrating pharmacogenomic data into routine care can improve patient safety in a cost-effective manner. The evolution from reactive single-gene testing to comprehensive pre-emptive genotyping panels holds great potential for refining drug prescribing practices. Several implementation projects have been conducted to test the feasibility of applying different genetic panels in clinical practice. Recently, the results of a large prospective randomized trial in Europe (the PREPARE study by Ubiquitous Pharmacogenomics consortium) have provided the first evidence that prospective application of a pre-emptive pharmacogenomic test panel in clinical practice, in seven European healthcare systems, is feasible and yielded a 30% reduction in the risk of developing clinically relevant toxicities. Nevertheless, some important questions remain unanswered and will hopefully be addressed by future dedicated studies. These issues include the cost-effectiveness of applying a pre-emptive genotyping panel, the role of multiple co-medications, the transferability of currently tested pharmacogenetic guidelines among patients of non-European origin and the impact of rare pharmacogenetic variants that are not detected by currently used genotyping approaches.
PubMed: 37926674
DOI: 10.1111/bcp.15956 -
Journal of Internal Medicine May 2024Pharmacogenomics is the examination of how genetic variation influences drug metabolism and response, in terms of both efficacy and safety. In cardiovascular disease,... (Review)
Review
Pharmacogenomics is the examination of how genetic variation influences drug metabolism and response, in terms of both efficacy and safety. In cardiovascular disease, patient-specific diplotypes determine phenotypes, thereby influencing the efficacy and safety of drug treatments, including statins, antiarrhythmics, anticoagulants and antiplatelets. Notably, polymorphisms in key genes, such as CYP2C9, CYP2C19, VKORC1 and SLCO1B1, significantly impact the outcomes of treatment with clopidogrel, warfarin and simvastatin. Furthermore, the CYP2C19 polymorphism influences the pharmacokinetics and safety of the novel hypertrophic cardiomyopathy inhibitor, mavacamten. In this review, we critically assess the clinical application of pharmacogenomics in cardiovascular disease and delineate present and future utilization of pharmacogenomics. This includes insights into identifying missing heritability, the integration of whole genome sequencing and the application of polygenic risk scores to enhance the precision of personalized drug therapy. Our discussion encompasses health economic analyses that underscore the cost benefits associated with pre-emptive genotyping for warfarin and clopidogrel treatments, albeit acknowledging the need for further research in this area. In summary, we contend that cardiovascular pharmacogenomic analyses are underpinned by a wealth of evidence, and implementation is already occurring for some of these gene-drug pairs, but as with any area of medicine, we need to continually gather more information to optimize the use of pharmacogenomics in clinical practice.
Topics: Humans; Precision Medicine; Warfarin; Pharmacogenomic Testing; Clopidogrel; Cytochrome P-450 CYP2C19; Cardiovascular Diseases; Anticoagulants; Pharmacogenetics; Liver-Specific Organic Anion Transporter 1; Vitamin K Epoxide Reductases
PubMed: 38343077
DOI: 10.1111/joim.13772 -
The Veterinary Clinics of North... Nov 2023Cardiomyopathies remain one of the most common inherited cardiac diseases in both human and veterinary patients. To date, well over 100 mutated genes are known to cause... (Review)
Review
Cardiomyopathies remain one of the most common inherited cardiac diseases in both human and veterinary patients. To date, well over 100 mutated genes are known to cause cardiomyopathies in humans with only a handful known in cats and dogs. This review highlights the need and use of personalized one-health approaches to cardiovascular case management and advancement in pharmacogenetic-based therapy in veterinary medicine. Personalized medicine holds promise in understanding the molecular basis of disease and ultimately will unlock the next generation of targeted novel pharmaceuticals and aid in the reversal of detrimental effects at a molecular level.
Topics: Humans; Animals; Cats; Dogs; Pets; Precision Medicine; Veterinary Drugs; Cardiomyopathies; Cardiology; Cat Diseases; Dog Diseases
PubMed: 37423841
DOI: 10.1016/j.cvsm.2023.05.016 -
Schizophrenia Research May 2024Schizophrenia is a highly heritable, severe mental illness characterized by hallucinations, delusions, social withdrawal, and cognitive dysfunction present in ∼1% of... (Review)
Review
Schizophrenia is a highly heritable, severe mental illness characterized by hallucinations, delusions, social withdrawal, and cognitive dysfunction present in ∼1% of populations across cultures. There have been recent major advancements in our understanding of the genetic architecture of schizophrenia. Both rare, highly penetrant genetic variants as well as common, low-penetrant genetic variants can predispose individuals to schizophrenia and can impact the way people metabolize psychoactive medications used to treat schizophrenia. However, the impact of these findings on the clinical management of schizophrenia remains limited. This review highlights the few places where genetics currently informs schizophrenia management strategies, discusses major limitations, and reviews promising areas of genetics research that are most likely to impact future schizophrenia care. Specifically, I focuss on psychiatric genetic counseling, genetic testing strategies, pharmacogenetics, polygenic risk, and genetics-guided treatment. Lastly, I emphasize important ethical considerations in the clinical use of genetics for schizophrenia management, including the exacerbation of healthcare inequalities and unintended consequences of new genetic technologies.
Topics: Humans; Schizophrenia; Pharmacogenetics; Genetic Testing; Genetic Counseling; Multifactorial Inheritance; Genetic Predisposition to Disease
PubMed: 37813777
DOI: 10.1016/j.schres.2023.09.042