A Comparison of Molecular Techniques for Improving the Methodology in the Laboratory of Pharmacogenetics.

One of the most critical goals in healthcare is safe and effective drug therapy, which is directly related to an individual's response to treatment. Precision medicine can improve drug safety in many scenarios, including polypharmacy, and it requires the development of new genetic characterization methods. In this report, we use real-time PCR, microarray techniques, and mass spectrometry (MALDI-TOF), which allows us to compare them and identify the potential benefits of technological improvements, leading to better quality medical care.

Variable Penetrance and Expressivity of a Rare Pore Loss-of-Function Mutation (p.L889V) of Nav1.5 Channels in Three Spanish Families.

A novel rare mutation in the pore region of Nav1.5 channels (p.L889V) has been found in three unrelated Spanish families that produces quite diverse phenotypic manifestations (Brugada syndrome, conduction disease, dilated cardiomyopathy, sinus node dysfunction, etc.

Importance of genetic study in elderly patients with transthyretin cardiac amyloidosis.

Background And Objective: Cardiac transthyretin amyloidosis (CA-ATTR) is a prevalent disease with age. Genetic study is recommended, even in eldest patients. We aim to analyze the prevalence of hereditary transthyretin amyloidosis (ATTRv) in elderly patients (≥75years) with CA-ATTR and its implications.

Case Report: Pharmacogenetics Applied to Precision Psychiatry Could Explain the Outcome of a Patient With a New Genotype.

Precision medicine applied to psychiatry provides new insight into the promising field of precision psychiatry. Psychotic disorders are heterogeneous, complex, chronic, and severe mental disorders. Not only does the prognosis and the course of the disease vary among patients suffering from psychotic disorders, but the treatment response varies as well.

Ten Years of Experience Support Pharmacogenetic Testing to Guide Individualized Drug Therapy.

Precision medicine utilizing the genetic information of genes involved in the metabolism and disposition of drugs can not only improve drug efficacy but also prevent or minimize adverse events. Polypharmacy is common among multimorbid patients and is associated with increased adverse events. One of the main objectives in health care is safe and efficacious drug therapy, which is directly correlated to the individual response to treatment.

Economic Impact of the Application of a Precision Medicine Model (5SPM) on Psychotic Patients.

Background: Schizophrenia is a severe mental disorder that often manifests within the first three decades of life. Its prognosis is uncertain and may result in a prolonged treatment that could extend throughout the entire lifespan of the patient. Antipsychotic drugs are characterized by a high interindividual variability when considering therapeutic effect and emergence of adverse effects.

A rare HCN4 variant with combined sinus bradycardia, left atrial dilatation, and hypertrabeculation/left ventricular noncompaction phenotype.

Introduction And Objectives: HCN4 variants have been reported to cause combined sick sinus syndrome (SSS) and left ventricular noncompaction (LVNC) cardiomyopathy. This relationship has been proven in few cases and no previous patients have associated left atrial dilatation (LAD). Our objective was to study a familial disorder characterized by SSS, LAD, and hypertrabeculation/LVNC and to identify the underlying genetic and electrophysiological characteristics.

Usefulness of Pharmacogenetic Analysis in Psychiatric Clinical Practice: A Case Report.

There are many factors involved in the effectiveness and efficiency of psychiatric drug treatment. One of them is psychotropic drug metabolism, which takes place mostly in the liver through the P450 enzyme system. However, there are genotypic variants of this system's enzymes that can directly affect both the efficacy and the onset of side effects of a given therapeutic regimen.

Comprehensive genomic diagnosis of non-syndromic and syndromic hereditary hearing loss in Spanish patients.

Background: Sensorineural hearing loss (SNHL) is the most common sensory impairment. Comprehensive next-generation sequencing (NGS) has become the standard for the etiological diagnosis of early-onset SNHL. However, accurate selection of target genomic regions (gene panel/exome/genome), analytical performance and variant interpretation remain relevant difficulties for its clinical implementation.

Pharmacogenetics and the treatment of asthma.

Heterogeneity defines both the natural history of asthma as well as patient's response to treatment. Pharmacogenomics contribute to understand the genetic basis of drug response and thus to define new therapeutic targets or molecular biomarkers to evaluate treatment effectiveness. This review is initially focused on different genes so far involved in the pharmacological response to asthma treatment.

Assessment and Validation of New Genetic Variants: A Systematic In Silico Approach.

The application of new high-throughput technologies to the study of asthma and other complex diseases is providing a huge amount of genetic information. Particularly, next-generation sequencing generates thousands of variants that have not been previously related to the studied diseases. These new genetic variants require validation both at methodological and clinical level.

Role of Pharmacogenetics in Improving the Safety of Psychiatric Care by Predicting the Potential Risks of Mania in CYP2D6 Poor Metabolizers Diagnosed With Bipolar Disorder.

One of the main concerns in psychiatric care is safety related to drug management. Pharmacogenetics provides an important tool to assess causes that may have contributed the adverse events during psychiatric therapy. This study illustrates the potential of pharmacogenetics to identify those patients for which pharmacogenetic-guided therapy could be appropriate.

Dose reduction of efavirenz: an observational study describing cost-effectiveness, pharmacokinetics and pharmacogenetics.

Aim: Antiretroviral treatment implies a high cost to the healthcare system. The aim of this study was to evaluate the clinical and economic impact of efavirenz (EFV) dose adjustment by monitoring plasma concentrations and pharmacogenetic analysis of the 516G>T CYP2B6 polymorphism.

Materials & Methods: One hundred and ninety HIV patients treated with EFV were studied.

Characterization of a complex CYP2D6 genotype that caused an AmpliChip CYP450 Test no-call in the clinical setting.

Background: CYP2D6, a major drug-metabolizing enzyme, is encoded by a highly polymorphic and complex gene locus. We have identified a patient who failed to produce a CYP2D6 genotype with the AmpliChip P450 Test (AmpliChip), whereas his CYP2C19 genotype was readily determined. The aim of this investigation was to fully characterize the patient's CYP2D6 gene locus to resolve the AmpliChip no-call.

Clinical evaluation of a microsphere bead-based flow cytometry assay for the simultaneous determination of anti-thyroid peroxidase and anti-thyroglobulin antibodies.

Objectives: Multiplexing technologies based on the use of microspheres as the solid phase have opened new possibilities for the analysis of autoantibodies. As an alternative to the traditional immunoassays, it is possible to use these methods in combination with flow cytometry for simultaneous measurement of anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibodies.

Design And Methods: We studied 127 serum samples sent to our laboratory for the quantitation of anti-TPO and anti-Tg antibodies.

Laboratory screening of connective tissue diseases by a new automated ENA screening assay (EliA Symphony) in clinically defined patients.

Background: The measurement of antinuclear antibodies (ANA) is used in the autoimmune laboratory for the screening of connective tissue diseases (CTD). ANA measurements are mainly performed by indirect immunofluorescence (IIF) on HEp-2 cells or by enzyme immunoassay (EIA). The objective of this study was to clinically evaluate an automated EIA for extractable nuclear antigens (ENA) which lacks anti-dsDNA for the screening of CTD.

Anti-cyclic citrullinated peptide autoantibodies in IgM rheumatoid factor-positive patients.

Background: Antibodies to citrullinated proteins have been described in patients with RA and these appear to be the most specific markers of the disease. The objective of this study was to analyse the improvement in diagnostic accuracy of anti-cyclic citrullinated peptide autoantibodies and IgA rheumatoid factor in patients with clinical suspicion of RA and who were IgM rheumatoid factor-positive. Anti-CCP antibodies were measured with three different second-generation enzyme immunoassays.

Clinical evaluation of cobas core anti-dsDNA EIA quant.

The measurement of antibodies to double-stranded DNA (anti-dsDNA) is a useful tool for the diagnosis and monitoring of patients with connective tissue diseases, particularly systemic lupus erythematosus (SLE). The aim of the present study was to compare a new enzyme-linked immunosorbent assay (ELISA) for the measurement of anti-dsDNA antibodies, which uses purified double-stranded plasmid DNA as the antigen (anti-dsDNA EIA Quant; Roche Diagnostics, Mannheim, Germany), with an established ELISA. The clinical usefulness of this new ELISA was also assessed.

Anti-nucleosome, anti-chromatin, anti-dsDNA and anti-histone antibody reactivity in systemic lupus erythematosus.

Anti-nucleosome (anti-chromatin) antibodies play a key role in the pathogenesis of systemic lupus erythematosus (SLE). The objective of the present study was to determine the clinical significance of anti-nucleosome (anti-chromatin) antibodies, anti-dsDNA antibodies and anti-histone antibodies in patients with SLE in relation to patients with positive nuclear antibodies and healthy controls. We measured anti-nucleosome (anti-chromatin) antibodies, anti-dsDNA antibodies and anti-histone antibodies in 70 patients with SLE, 35 antinuclear antibody (ANA)-positive subjects without autoimmune disease and 35 blood donors.