MIR27A rs895819 CC Genotype Severely Reduces miR-27a Plasma Expression Levels.

rs895819 polymorphism has emerged as a potential additional pharmacogenomic marker of fluoropyrimidine response. Current evidence on its potential effect on miR-27a expression, which represses DPD activity, leading to DPD deficiency and increased fluoropyrimidine-associated toxicity risk, is scarce and inconsistent. We have analyzed the effect of rs895819 polymorphism on miR-27a-3p plasma expression levels under different models of inheritance to contribute further evidence on its plausible biological role in miR-27a expression.

Circulating microRNAs and DNA Methylation as Regulators of Direct Oral Anticoagulant Response in Atrial Fibrillation and Key Elements for the Identification of the Mechanism of Action (miR-CRAFT): Study Design and Patient Enrolment.

Direct oral anticoagulants (DOACs) are the standard treatment for thromboembolic protection in atrial fibrillation (AF) patients. Epigenetic modifications, such as DNA methylation and microRNAs, have emerged as potential biomarkers of AF. The epigenetics of DOACs is still an understudied field.

Genetic diversity of cytochrome P450 in patients receiving psychiatric care in Greece: a step towards clinical implementation.

We herein inferred the genetic diversity of CYP450 isoenzymes to predict the percentage of patients who need dose adjustment in drugs used in psychiatry. Data of 784 Greek patients receiving psychiatric care who were genotyped for CYP2D6, CYP2C19, CYP1A2, CYP3A5 and CYP2C9 isoenzymes were inferred to gene-drug pairs according to the US FDA, Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetics Working Group annotations and published literature. Atypical metabolism was found for 36.

Fluoropyrimidine Toxicity: the Hidden Secrets of DPYD.

Background: Fluoropyrimidine-induced toxicity is a main limitation of therapy. Currently, polymorphisms in the DPYD gene, which encodes the 5-FU activation enzyme dihydropyrimidine dehydrogenase (DPD), are used to adjust the dosage and prevent toxicity. Despite the predictive value of DPYD genotyping, a great proportion of fluoropyrimidine toxicity cannot be solely explained by DPYD variations.

rs895819 TC genotype increases risk of fluoropyrimidine-induced severe toxicity independently of variations.

MicroRNA 27a (miR-27a) regulates post-transcriptionally DPD activity. We have analyzed the association of rs895819T>C variation, that modulates miR-27a expression, with fluropyrimidine-induced toxicity. rs895819T>C genotyping was conducted by TaqMan® allelic discrimination assay in 313 FP-treated cancer patients.

Polymorphisms in LRP2 and CUBN genes and their association with serum vitamin D levels and sleep apnea.

Purpose: Vitamin D deficiency has been associated with the occurrence of obstructive sleep apnea syndrome (OSAS). Megalin (LRP2) and cubilin (CUBN) are implicated in vitamin D metabolism, whereas LRP2 and CUBN polymorphisms have been previously associated with variable serum vitamin D levels. The present study aimed to evaluate the role of LRP2 rs2228171 c.

Beyond the Rhythm: In Silico Identification of Key Genes and Therapeutic Targets in Atrial Fibrillation.

Atrial fibrillation (AF) is a prevalent cardiac arrhythmia worldwide and is characterized by a high risk of thromboembolism, ischemic stroke, and fatality. The precise molecular mechanisms of AF pathogenesis remain unclear. The purpose of this study was to use bioinformatics tools to identify novel key genes in AF, provide deeper insights into the molecular pathogenesis of AF, and uncover potential therapeutic targets.

Distinct pleiotropic effects of direct oral anticoagulants on cultured endothelial cells: a comprehensive review.

Direct Oral Anticoagulants (DOACs) have simplified the treatment of thromboembolic disease. In addition to their established anticoagulant effects, there are indications from clinical and preclinical studies that DOACs exhibit also non-anticoagulant actions, such as anti-inflammatory and anti-oxidant actions, advocating overall cardiovascular protection. In the present study, we provide a comprehensive overview of the existing knowledge on the pleiotropic effects of DOACs on endothelial cells (ECs) and their underlying mechanisms, while also identifying potential differences among DOACs.

Implementing pharmacogenetic testing in fluoropyrimidine-treated cancer patients: genotyping to guide chemotherapy dosing in Greece.

Dihydropyrimidine dehydrogenase (DPD), encoded by gene, is the rate-limiting enzyme responsible for fluoropyrimidine (FP) catabolism. gene variants seriously affect DPD activity and are well validated predictors of FP-associated toxicity. variants rs3918290, rs55886062, rs67376798, and rs75017182 are currently included in FP genetic-based dosing guidelines and are recommended for genotyping by the European Medicines Agency (EMA) before treatment initiation.

Therapeutic Drug Monitoring (TDM) Implementation in Public Hospitals in Greece in 2003 and 2021: A Comparative Analysis of TDM Evolution over the Years.

Therapeutic drug monitoring (TDM) is the clinical practice of measuring drug concentrations. TDM can be used to determine treatment efficacy and to prevent the occurrence or reduce the risk of drug-induced side effects, being, thus, a tool of personalized medicine. Drugs for which TDM is applied should have a narrow therapeutic range and exhibit both significant pharmacokinetic variability and a predefined target concentration range.

Pharmacogenomic-guided dosing of fluoropyrimidines beyond : time for a polygenic algorithm?

Fluoropyrimidines are chemotherapeutic agents widely used for the treatment of various solid tumors. Commonly prescribed FPs include 5-fluorouracil (5-FU) and its oral prodrugs capecitabine (CAP) and tegafur. Bioconversion of 5-FU prodrugs to 5-FU and subsequent metabolic activation of 5-FU are required for the formation of fluorodeoxyuridine triphosphate (FdUTP) and fluorouridine triphosphate, the active nucleotides through which 5-FU exerts its antimetabolite actions.

Multi-omics integration to identify the genetic expression and protein signature of dilated and ischemic cardiomyopathy.

Introduction: Heart failure (HF) is a complex clinical syndrome leading to high morbidity. In this study, we aimed to identify the gene expression and protein signature of HF main causes, namely dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM).

Methods: Omics data were accessed through GEO repository for transcriptomic and PRIDE repository for proteomic datasets.

The revolution of pharmaco-omics: ready to open new avenues in materializing precision medicine?

Tweetable abstract The pharmaco-omics revolution has started and, as a wild stream, sooner or later, will expand and dramatically improve drug discovery and individual response to pharmacotherapy. Hopefully, we will all be ready to follow the stream.

Unpacking COVID-19 Systems Biology in Lung and Whole Blood with Transcriptomics and miRNA Regulators.

COVID-19 is a systemic disease affecting tissues and organs, including and beyond the lung. Apart from the current pandemic context, we also have vastly inadequate knowledge of consequences of repeated exposures to SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the virus causing COVID-19, in multiple organ systems and the whole organism scales when the disease evolves from a pandemic to an endemic state. This calls for a systems biology and systems medicine approach and unpacking the effects of COVID-19 in lung as well as other tissues.

c.521T>C gene polymorphism decreases hypoglycemia risk in sulfonylurea-treated type 2 diabetic patients.

Objectives: Pharmacogenomics can explain some of the heterogeneity of sulfonylurea (SU)-related hypoglycemia risk. Recently, a role of OATP1B1, encoded by gene, on SU liver transport prior of metabolism has been uncovered. The aim of the present study was to explore the potential association of c.

c.665C>T guided fluoropyrimidine therapy in cancer: gender-dependent effect on dose requirements.

Objectives: The fluoropyrimidine derivatives 5-Fluorouracil and Capecitabine are widely used for the treatment of solid tumors. Fluoropyrimidine metabolism involves a cascade of different enzymes, including MTHFR enzyme. c.

Gender-dependent association of -TSER polymorphism with 5-fluorouracil or capecitabine-based chemotherapy toxicity.

gene encodes for TS enzyme involved in 5-fluorouracil (5-FU) and capecitabine (CAP) metabolism. This study assessed the association of -TSER and 3RG>C polymorphisms with 5-FU/CAP adverse event (AE) incidence. -TSER and 3RG>C polymorphisms were analyzed by use of PCR/PCR-RFLP in 313 5-FU/CAP-treated cancer patients.

TCF7L2 rs7903146 C>T gene polymorphism is not associated with hypoglycemia in sulfonylurea-treated type 2 diabetic patients.

Objectives: Hypoglycemia is the most common adverse effect of sulfonylureas (SUs) and a major concern when using these drugs. Transcription factor 7-like 2 (TCF7L2) rs7903146 C>T polymorphism is an established and well characterized genetic marker of type 2 diabetes (T2DM) risk. The aim of the present study was to analyze the potential association of TCF7L2 rs7903146 C>T polymorphism with SU-induced hypoglycemia in a well characterized cohort of SU-treated patients previously genotyped for cytochrome P450 2C9 (CYP2C9) and P450 oxidoreductase (POR).

Assessing COVID-19 susceptibility through analysis of the genetic and epigenetic diversity of ACE2-mediated SARS-CoV-2 entry.

There is considerable variation in disease course among individuals infected with SARS-CoV-2. Many of them do not exhibit any symptoms, while some others proceed to develop COVID-19; however, severity of COVID-19 symptoms greatly differs among individuals. Focusing on the early events related to SARS-CoV-2 entry to cells through the ACE2 pathway, we describe how variability in (epi)genetic factors can conceivably explain variability in disease course.

Inhibition of SARS-CoV-2 entry through the ACE2/TMPRSS2 pathway: a promising approach for uncovering early COVID-19 drug therapies.

Aim: The COVID-19 pandemic caused by infection with the novel coronavirus SARS-CoV-2 is urging the scientific community worldwide to intense efforts for identifying and developing effective drugs and pharmacologic strategies to treat the disease. Many of the drugs that are currently in (pre)clinical development are addressing late symptoms of the disease. This review focuses on potential pharmacologic intervention at an early stage of infection which could result in less-infected individuals and less cases with severe COVID-19 disease due to reduced virus entry into the cells.

Endothelial nitric oxide synthase gene polymorphisms are associated with sensitization to seasonal aeroallergens in asthmatic children.

Background: Childhood asthma phenotype is the consequence of interaction between environment and genetic factors. Nitric oxide (NO) formation is affected by polymorphisms in nitric oxide synthase (NOS) enzymes, which play a significant role as inflammatory factors in the airways. This study was undertaken to estimate the correlation of -786C>T and 894G>T polymorphisms of the eNOS gene with the sensitization of asthmatic children to common aeroallergens.

Pharmacokinetic interactions of selective serotonin reuptake inhibitors with other commonly prescribed drugs in the era of pharmacogenomics.

Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed to treat depression and a broad range of other comorbidities. The increased use of SSRIs in patients with various comorbidities treated with different drugs engenders the risk of pharmacokinetic drug interactions via cytochrome P450 (CYP450) enzymes inhibition. In the present review, we provide an overview of documented clinically significant drug interactions between SSRIs and other drugs co-prescribed in psychiatric patients for the same or other diseases.

The -759C/T polymorphism of the 5-HT2C receptor is associated with type 2 diabetes in male and female Caucasians.

Objectives: Type 2 diabetes mellitus and obesity constitute serious health problems. Studies reveal that the 5-HT2C receptor contributes substantially to the regulation of a wide variety of behavioral and physiological processes including feeding and glucose homeostasis. Our aim was to determine the possible association of the -759C/T polymorphism of the 5-HT2C receptor gene with type 2 diabetes and obesity in male and female individuals Caucasian origin.