pharmacoepigenetics

Aim: To explore possible differences in genome-wide methylation between schizophrenia patients who consume various antipsychotics. Methods: We compared DNA methylation in leukocytes between the following cohorts: clozapine (n = 19) versus risperidone (n = 19), clozapine (n = 12) versus olanzapine (n = 12), clozapine (n = 9) versus quetiapine (n = 9) and clozapine (n = 33) versus healthy controls (n = 33). Subjects were matched for age, sex, ethnicity, smoking status and leukocyte proportions...

INTRODUCTION: Anxiety disorders (AD) are among the most common mental disorders worldwide. Pharmacotherapy, including benzodiazepines, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and tricyclic antidepressants is currently based on "trial-and-error", and is effective in a subset of patients or produces partial response only. Recent research proposes that treatment response and tolerability of the drugs are associated with genetic factors. AREAS COVERED: In the present review, we provide information on pharmacogenetics (PGx) in AD, including pharmacokinetic and pharmacodynamic genes...

The term 'epigenetics' refers to a series of meiotically/mitotically inheritable alterations in gene expression, related to environmental factors, without disruption on DNA sequences of bases. Recently, the pathophysiology of autoimmune diseases (ADs) has been closely linked to epigenetic modifications. In fact, epigenetic mechanisms can modulate gene expression or repression of targeted cells and tissues involved in autoimmune/inflammatory conditions acting as keys effectors in regulation of adaptive and innate responses...

INTRODUCTION: Juvenile idiopathic arthritis (JIA) is a chronic disease characterized by persistent joint inflammation. JIA is the most common pediatric chronic rheumatic disease and no curative therapy is currently available. Methotrexate (MTX) is an important treatment for JIA even though a high inter-individual variability in response is observed in patients. Among the factors of this variability, genetics and epigenetics might play an important role. AREAS COVERED: This review summarizes the results of pharmacogenetic and pharmacoepigenetic studies regarding MTX response in JIA...

Polymorphisms in genes associated with opioid signaling and dopamine reuptake and inactivation may moderate naltrexone efficacy in Alcohol Use Disorder (AUD), but the effects of epigenetic modification of these genes on naltrexone response are largely unexplored. This study tested interactions between methylation in the μ-opioid receptor (OPRM1), dopamine transporter (SLC6A3), and catechol-O-methyltransferase (COMT) genes as predictors of naltrexone effects on heavy drinking in a 16-week randomized, placebo-controlled trial among 145 treatment-seeking AUD patients...

Interactions of drugs with the classical epigenetic mechanism of DNA methylation or histone modification are increasingly being elucidated mechanistically and used to develop novel classes of epigenetic therapeutics. A data science approach is used to synthesize current knowledge on the pharmacological implications of epigenetic regulation of gene expression. Computer-aided knowledge discovery for epigenetic implications of current approved or investigational drugs was performed by querying information from multiple publicly available gold-standard sources to (i) identify enzymes involved in classical epigenetic processes, (ii) screen original biomedical scientific publications including bibliometric analyses, (iii) identify drugs that interact with epigenetic enzymes, including their additional non-epigenetic targets, and (iv) analyze computational functional genomics of drugs with epigenetic interactions...

Atremorine is a novel bioproduct obtained by nondenaturing biotechnological processes from a genetic species of Vicia faba. Atremorine is a potent dopamine (DA) enhancer with powerful effects on the neuronal dopaminergic system, acting as a neuroprotective agent in Parkinson's disease (PD). Over 97% of PD patients respond to a single dose of Atremorine (5 g, p.o.) 1 h after administration. This response is gender-, time-, dose-, and genotype-dependent, with optimal doses ranging from 5 to 20 g/day, depending upon disease severity and concomitant medication...

Pharmacotherapy is the most common treatment for schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). Pharmacogenetic studies have achieved results with limited clinical utility. DNA methylation (DNAm), an epigenetic modification, has been proposed to be involved in both the pathology and drug treatment of these disorders. Emerging data indicates that DNAm could be used as a predictor of drug response for psychiatric disorders. In this study, we performed a systematic review to evaluate the reproducibility of published changes of drug response-related DNAm in SCZ, BD and MDD...

Schizophrenia is a complex psychiatric disorder where genetic, epigenetic, and environmental factors play a role in disease onset, course of illness, and treatment outcome. Pharmaco(epi)genetic research presents an important opportunity to improve patient care through prediction of medication side effects and response. In this narrative review, we discuss the current state of research and important progress of both genetic and epigenetic factors involved in antipsychotic response, over the past five years. The review is largely focused on the following frequently prescribed antipsychotics: olanzapine, risperidone, aripiprazole, and clozapine...

Aim: Statins lower cholesterol and reduce the risk of cardiovascular disease. However, the exact mechanisms of statins remain unknown. We investigated whether statin therapy associates with epigenetics in Type 2 diabetes (T2D) patients. Materials & methods: DNA methylation was analyzed in blood from newly diagnosed T2D patients in All New Diabetics in Scania (ANDIS) and a replication cohort All New Diabetics in Uppsala County (ANDiU). Results: Seventy-nine sites were differentially methylated between cases on statins and controls (false discovery rate <5%) in ANDIS...

When used during pregnancy, analgesics and psychotropics pass the placenta to enter the foetal circulation and may induce epigenetic modifications. Where such modifications occur and whether they disrupt normal foetal developme nt, are currently unanswered questions. This field of prenatal pharmacoepigenetics has received increasing attention, with several studies reporting associations between in utero medication exposure and offspring epigenetic outcomes. Nevertheless, no recent systematic review of the literature is available...

BACKGROUND: COMT had been considered a promising candidate gene in pharmacogenetic studies in ADHD; yet the findings from these studies have been inconsistent. Part of these inconsistencies could be related to epigenetic mechanisms (including DNA methylation). Here we investigated the role of genetic variants of the COMT gene on the methylation levels of CpG sites in the same gene and explored the effect of methylation on methylphenidate (MPH) and placebo (PBO) response in children with ADHD...

The FOLFOX scheme, based on the association of 5-fluorouracil and oxaliplatin, is the most frequently indicated chemotherapy scheme for patients diagnosed with metastatic colorectal cancer. Nevertheless, development of chemoresistance is one of the major challenges associated with this disease. It has been reported that epithelial-mesenchymal transition (EMT) is implicated in microRNA-driven modulation of tumor cells response to 5-fluorouracil and oxaliplatin. Moreover, from pharmacogenomic research, it is known that overexpression of genes encoding dihydropyrimidine dehydrogenase ( DPYD ), thymidylate synthase ( TYMS ), methylenetetrahydrofolate reductase ( MTHFR ), the DNA repair enzymes ERCC1 , ERCC2 , and XRCC1 , and the phase 2 enzyme GSTP1 impair the response to FOLFOX...

Glucocorticoids (GCs) are commonly used as therapeutic agents for immune-mediated diseases and leukemia. However, considerable inter-individual differences in efficacy have been reported. Several reports indicate that the inhibitor of mTOR rapamycin can reverse GC resistance, but the molecular mechanism involved in this synergistic effect has not been fully defined. In this context, we explored the differential miRNA expression in a GC-resistant CCRF-CEM cell line after treatment with rapamycin alone or in co-treatment with methylprednisolone (MP)...

Symptomatic interventions for patients with dementia involve anti-dementia drugs to improve cognition, psychotropic drugs for the treatment of behavioral disorders (BDs), and different categories of drugs for concomitant disorders. Demented patients may take >6-10 drugs/day with the consequent risk for drug-drug interactions and adverse drug reactions (ADRs >80%) which accelerate cognitive decline. The pharmacoepigenetic machinery is integrated by pathogenic, mechanistic, metabolic, transporter, and pleiotropic genes redundantly and promiscuously regulated by epigenetic mechanisms...

Alzheimer's disease (AD) has been clinically characterized by a progressive degeneration of neurons which resulted in a gradual and irreversible cognitive impairment. The accumulation of A β and τ proteins in the brain contribute to the severity of the disease. Recently, vitexin compound has been the talk amongst researchers due to its pharmacological properties as anti-inflammation and anti-AD. However, the epigenetic mechanism of the compound in regulating the neuroinflammation activity is yet to be fully elucidated...

The pharmacoepigenetics of antipsychotic treatment in severe mental illness is a growing area of research that aims to understand the interface between antipsychotic treatment and genetic regulation. Pharmacoepigenetics may some day assist in identifying treatment response mechanisms or become one of the components in the implementation of precision medicine. To understand the current evidence regarding the effects of antipsychotics on DNA methylation a systematic review with qualitative synthesis was performed through Pubmed, Embase and Psychinfo from earliest data to June 2019...

Personalized drug therapy aims to provide tailored treatment for individual patient. Mass spectrometry (MS) is revolutionarily involved in this area because MS is a rapid, customizable, cost-effective, and easy to be used high-throughput method with high sensitivity, specificity, and accuracy. It is driving the formation of a new field, MS-based personalized drug therapy, which currently mainly includes five subfields: therapeutic drug monitoring (TDM), pharmacogenomics (PGx), pharmacomicrobiomics, pharmacoepigenomics, and immunopeptidomics...

Cardiovascular diseases are the number one cause of death worldwide and greatly impact quality of life and medical costs. Enormous effort has been made in research to obtain new tools for efficient and quick diagnosis and predicting the prognosis of these diseases. Discoveries of epigenetic mechanisms have related several pathologies, including cardiovascular diseases, to epigenetic dysregulation. This has implications on disease progression and is the basis for new preventive strategies. Advances in methodology and big data analysis have identified novel mechanisms and targets involved in numerous diseases, allowing more individualized epigenetic maps for personalized diagnosis and treatment...

Introduction : Alzheimer's disease (AD) vaccination is one of the last therapeutic options after two decades of stagnation in terms of drug development. About 140 (85%) immunization procedures against Aβ deposition and 25 (15%) against Tau have been reported, but no Food and Drug Administration approval of any AD vaccine has been achieved. This might be attributed to deficient pathogenic targets, inappropriate models, defective immunotherapeutic procedures, and inadequate clinical trial design. Areas covered : The issues covered include the following: AD pathogenic mechanisms, rationale for active and passive immunization, vaccine targets, anti-Aβ/Tau vaccines, vaccine technologies, animal models, and clinical trials...