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Annals of Medicine Dec 2020Statins are the first-line choice in Lipid-lowering therapy to reduce cardiovascular risk. In a continuous attempt to optimise treatment success, there is a need for... (Review)
Review
Statins are the first-line choice in Lipid-lowering therapy to reduce cardiovascular risk. In a continuous attempt to optimise treatment success, there is a need for additional research on genes and related molecular pathways that can determine the efficacy and toxicity of lipid-lowering drugs. Several variations within genes associated with lipid metabolism, including those involved in uptake, distribution and metabolism of statins have been reported. The purpose of this study was to evaluate the effect of genetic variations in the key genes responsible for statins' metabolism and their role in personalised medicine and pharmacogenetic testing (PGx) in patients treated with such drugs. Genetic assessment for specific known SNPs within the most known genes such as , and , appears likely to predict the efficacy of statin therapy and prevent their side effects but does not necessarily reduce the risk of cardiovascular events. Key Messages Hypercholesterolaemia patients show different response to statin therapy. Several variations within genes associated with statin metabolism have been investigated. Genetic assessment for specific known SNPs within the most known genes may improve the efficacy of statins treatment and prevent their side effects.
Topics: ATP Binding Cassette Transporter, Subfamily G, Member 2; Cardiovascular Diseases; Cytochrome P-450 CYP3A; Feasibility Studies; Humans; Hydroxymethylglutaryl CoA Reductases; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Liver-Specific Organic Anion Transporter 1; Neoplasm Proteins; Pharmacogenomic Testing; Pharmacogenomic Variants; Polymorphism, Single Nucleotide; Precision Medicine; Prognosis; Risk Assessment; Treatment Outcome
PubMed: 32735150
DOI: 10.1080/07853890.2020.1800074 -
Human Molecular Genetics May 2018The field of pharmacogenomics is an area of great potential for near-term human health impacts from the big genomic data revolution. Pharmacogenomics research momentum... (Review)
Review
The field of pharmacogenomics is an area of great potential for near-term human health impacts from the big genomic data revolution. Pharmacogenomics research momentum is building with numerous hypotheses currently being investigated through the integration of molecular profiles of different cell lines and large genomic data sets containing information on cellular and human responses to therapies. Additionally, the results of previous pharmacogenetic research efforts have been formulated into clinical guidelines that are beginning to impact how healthcare is conducted on the level of the individual patient. This trend will only continue with the recent release of new datasets containing linked genotype and electronic medical record data. This review discusses key resources available for pharmacogenomics and pharmacogenetics research and highlights recent work within the field.
Topics: Big Data; Genomics; Genotype; Humans; Pharmacogenetics; Pharmacogenomic Testing
PubMed: 29635477
DOI: 10.1093/hmg/ddy116 -
PLoS Genetics Apr 2019The promise of personalized genomic medicine is that knowledge of a person's gene sequences and activity will facilitate more appropriate medical interventions,... (Review)
Review
The promise of personalized genomic medicine is that knowledge of a person's gene sequences and activity will facilitate more appropriate medical interventions, particularly drug prescriptions, to reduce the burden of disease. Early successes in oncology and pediatrics have affirmed the power of positive diagnosis and are mostly based on detection of one or a few mutations that drive the specific pathology. However, genetically more complex diseases require the development of polygenic risk scores (PRSs) that have variable accuracy. The rarity of events often means that they have necessarily low precision: many called positives are actually not at risk, and only a fraction of cases are prevented by targeted therapy. In some situations, negative prediction may better define the population at low risk. Here, I review five conditions across a broad spectrum of chronic disease (opioid pain medication, hypertension, type 2 diabetes, major depression, and osteoporotic bone fracture), considering in each case how genetic prediction might be used to target drug prescription. This leads to a call for more research designed to evaluate genetic likelihood of response to therapy and a call for evaluation of PRS, not just in terms of sensitivity and specificity but also with respect to potential clinical efficacy.
Topics: Depressive Disorder, Major; Diabetes Mellitus, Type 2; Female; Humans; Hypertension; Male; Multifactorial Inheritance; Mutation; Opioid-Related Disorders; Osteoporosis; Pharmacogenomic Testing; Precision Medicine; Preventive Medicine; Risk Factors
PubMed: 31022172
DOI: 10.1371/journal.pgen.1008060 -
Journal of Developmental and Behavioral...This study investigated outcomes of pharmacogenetic testing of youth with autism spectrum disorder (ASD) referred to a precision medicine clinic and explored...
OBJECTIVE
This study investigated outcomes of pharmacogenetic testing of youth with autism spectrum disorder (ASD) referred to a precision medicine clinic and explored associations between patient characteristics and pharmacogenomic testing results.
METHODS
Records for patients diagnosed with ASD and subsequently referred to a pediatric hospital's precision medicine clinic between July 1, 2010, and June 30, 2020, were reviewed. Pharmacogenetic testing results were abstracted focusing on CYP2D6 and CYP2C19. In addition, we compiled counts of patients' co-occurring diagnoses, histories of adverse drug reactions (ADRs), previously trialed ineffective medications, and previous psychiatric medication changes. Logistic regression models were fit to examine CYP2C19 and CYP2D6 metabolizer status as functions of patient demographics and prereferral medication histories.
RESULTS
Of 202 patients (mean age = 12.18 yrs), 66% were referred to precision medicine because of poor medication response. Among patients with pharmacogenomic testing results for CYP2D6, 9% were classified as poor metabolizers; among patients with results for CYP2C19, 10% were classified as rapid/ultrarapid metabolizers. Patient demographics and medication response history did not predict pharmacogenomic results. However, the number of co-occurring diagnoses positively predicted the number of nonpsychiatric ADRs and a higher probability of CYP2D6 poor metabolizer status; moreover, nonpsychiatric ADRs positively predicted CYP2C19 rapid/ultrarapid metabolizer status.
CONCLUSION
In one of the largest reported samples of youth with ASD clinically referred for pharmacogenetic testing, we observed high variability in medication response and yield for actionable results. Our findings suggest potential clinical utility for pharmacogenetic testing and introduce possible clinical profiles associated with metabolizer status.
Topics: Child; Adolescent; Humans; Cytochrome P-450 CYP2D6; Precision Medicine; Cytochrome P-450 CYP2C19; Pharmacogenomic Testing; Autism Spectrum Disorder; Genotype
PubMed: 37807195
DOI: 10.1097/DBP.0000000000001215 -
The Pharmacogenomics Journal May 2022United States clinical practice guidelines for metastatic colorectal cancer recommend use of medications impacted by genetic variants but do not recommend testing. We...
United States clinical practice guidelines for metastatic colorectal cancer recommend use of medications impacted by genetic variants but do not recommend testing. We analyzed real-world treatment using a cancer registry and claims dataset to explore pharmacogenomic (PGx) medication treatment patterns and characterize exposure. In a cohort of 6957 patients, most (86.9%) were exposed to at least one chemotherapy medication with PGx guidelines. In a cohort of 2223 patients with retail pharmacy claims available, most (79.2%) were treated with at least one non-chemotherapy (79.2%) medication with PGx guidelines. PGx-associated chemotherapy exposure was associated with age, race/ethnicity, educational attainment, and rurality. PGx-associated non-chemotherapy exposure was associated with medication use and comorbidities. The potential impact of PGx testing is large and policies aimed at increasing PGx testing at diagnosis may impact treatment decisions for patients with metastatic colorectal cancer as most patients are exposed to medications with pharmacogenomics implications during treatment.
Topics: Aged; Cohort Studies; Colorectal Neoplasms; Ethnicity; Humans; Medicare; Pharmacogenetics; Pharmacogenomic Testing; United States
PubMed: 35361994
DOI: 10.1038/s41397-022-00276-6 -
BioTechniques Jan 2020Francesca Lake explores the latest goings on in techniques advancing precision medicine.
Francesca Lake explores the latest goings on in techniques advancing precision medicine.
Topics: Genome, Human; Host-Pathogen Interactions; Humans; Information Dissemination; Neoplasms; Periodicals as Topic; Pharmacogenomic Testing; Precision Medicine; Translational Research, Biomedical
PubMed: 31849238
DOI: 10.2144/btn-2019-0163 -
BMC Psychiatry May 2023Pharmacogenomic testing guided treatment have been developed to guide drug selection or conversion in major depressive disorder patients. Whether patients benefit from... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pharmacogenomic testing guided treatment have been developed to guide drug selection or conversion in major depressive disorder patients. Whether patients benefit from pharmacogenetic testing remains unclear. We aim to evaluates the effect of pharmacogenomic testing guiding on clinical outcomes of major depressive disorder.
METHODS
Pubmed, Embase, and Cochrane Library of Clinical Trials were searched from inception until August 2022. Key terms included pharmacogenomic and antidepressive. Odds ratios (RR) with 95% confidence intervals (95%CIs) were calculated using fixed-effects model for low or moderate heterogeneity or random-effects model for high heterogeneity.
RESULTS
Eleven studies (5347 patients) were included. Compared with usual group, pharmacogenomic testing guided group was associated with an increased response rate at week 8 (OR 1.32, 95%CI 1.15-1.53, 8 studies, 4328 participants) and week 12 (OR 1.36, 95%CI 1.15-1.62, 4 studies, 2814 participants). Similarly, guided group was associated with an increased rate of remission at week 8 (OR 1.58, 95%CI 1.31-1.92, 8 studies, 3971 participants) and week 12 (OR 2.23, 95%CI 1.23-4.04, 5 studies, 2664 participants). However, no significant differences were found between the two groups in response rate at week 4 (OR 1.12, 95%CI 0.89-1.41, 2 studies, 2261 participants) and week 24 (OR 1.16, 95%CI 0.96-1.41, 2 studies, 2252 participants), and remission rate at week 4 (OR 1.26, 95%CI 0.93-1.72, 2 studies, 2261 participants) and week 24 (OR 1.06, 95%CI 0.83-1.34, 2 studies, 2252 participants). Medication congruence in 30 days was significantly reduced in the pharmacogenomic guided group compared with the usual care group (OR 2.07, 95%CI 1.69-2.54, 3 studies, 2862 participants). We found significant differences between subgroups of target population in response and remission rate.
CONCLUSION
Patients with major depressive disorder may benefit from pharmacogenomic testing guided treatment by achieving target response and remission rates more quickly.
Topics: Humans; Depressive Disorder, Major; Pharmacogenetics; Antidepressive Agents; Pharmacogenomic Testing; Odds Ratio; Randomized Controlled Trials as Topic
PubMed: 37173736
DOI: 10.1186/s12888-023-04756-2 -
Pharmacogenetics and Genomics Dec 2020The emergency department (ED) is a challenging setting to conduct pharmacogenomic studies and integrate that data into fast-paced and potentially life-saving treatment...
OBJECTIVES
The emergency department (ED) is a challenging setting to conduct pharmacogenomic studies and integrate that data into fast-paced and potentially life-saving treatment decisions. Therefore, our objective is to present the methods and feasibility of a pilot pharmacogenomic study set in the ED that measured pediatric bronchodilator response (BDR) during acute asthma exacerbations.
METHODS
This is an exploratory pilot study that collected buccal swabs for DNA and measured BDR during ED encounters for pediatric asthma exacerbations. We evaluated the study's feasibility with a qualitative analysis of ED provider surveys and quantitatively by the proportion of eligible patients enrolled.
RESULTS
We enrolled 59 out of 90 patients (65%) that were identified and considered eligible during a 5-month period (target enrollment 60 patients over 12 months). The median patient age was 7 years (interquartile range 4-9 years), 61% (N = 36) were male, and 92% (N = 54) were African American. Quality DNA collection was successful for all 59 patients. The ED provider survey response rate was 100%. Most ED providers reported that the study did not impact their workflow (98% of physicians, 88% of nurses, and 90% of respiratory therapists). ED providers did report difficulties with spirometry in the younger age group.
CONCLUSIONS
Pharmacogenomic studies can be conducted in the ED setting, and enroll a younger patient population with a high proportion of minority participants. By disseminating this study's methods and feasibility analysis, we aim to increase interest in pharmacogenomic studies set in the ED and aimed toward future ED-based pharmacogenomic decision-making.
Topics: Adolescent; Asthma; Child; Child, Preschool; Delivery of Health Care; Emergency Service, Hospital; Female; Follow-Up Studies; Health Plan Implementation; Humans; Male; Pharmacogenomic Testing; Physicians; Pilot Projects; Practice Guidelines as Topic; Prognosis; Surveys and Questionnaires
PubMed: 33017130
DOI: 10.1097/FPC.0000000000000414 -
Personalized Medicine Mar 2022Patient knowledge and attitudes toward pharmacogenetic (PGx) testing may impact adoption of clinical testing. Questionnaires regarding knowledge, attitudes and ethics...
Patient knowledge and attitudes toward pharmacogenetic (PGx) testing may impact adoption of clinical testing. Questionnaires regarding knowledge, attitudes and ethics of PGx testing were distributed to 504 patients enrolled in the ADAPT study conducted at two urban hospitals in Philadelphia, Pennsylvania, USA. Responses were assessed using multivariable logistic regression. 311 completed the survey (62% response rate). 74% were unaware of PGx testing, but 79% indicated using PGx results to predict medication efficacy was important. In a multivariable model, higher education level (p = 0.031) and greater genetics knowledge (p < 0.001) were associated with more positive attitudes toward PGx testing. Greater patient knowledge of genetics was associated with a more positive attitude toward PGx testing, indicating that educational strategies aimed at increasing genetics knowledge may enhance adoption of PGx testing in the clinic.
Topics: Attitude; Cytochrome P-450 CYP2C19; Humans; Percutaneous Coronary Intervention; Pharmacogenetics; Pharmacogenomic Testing
PubMed: 34984913
DOI: 10.2217/pme-2021-0064 -
Molecular Diagnosis & Therapy Jan 2022On the basis of scientific evidence, information on the option, recommendation or requirement to test for pharmacogenetic or pharmacogenomic biomarkers is incorporated... (Review)
Review
On the basis of scientific evidence, information on the option, recommendation or requirement to test for pharmacogenetic or pharmacogenomic biomarkers is incorporated in the Summary of Product Characteristics of an increasing number of drugs in Europe. A screening of the Genetic Testing Registry (GTR) showed that a variety of molecular genetic testing methods is currently offered worldwide in testing services with regard to according drugs and biomarkers. Thereby, among the methodology indicated in the screened GTR category 'Molecular Genetics', next-generation sequencing is applied for identification of the largest proportion of evaluated biomarkers that are relevant for therapeutic management of centrally approved drugs in Europe. However, sufficient information on regulatory clearances, clinical utility, analytical and clinical validity of applied methods is rarely provided.
Topics: Biomarkers; Europe; Genetic Testing; Humans; Pharmacogenetics; Pharmacogenomic Testing
PubMed: 34905151
DOI: 10.1007/s40291-021-00567-x