Periconceptional Non-medical Maternal Determinants Influence the Tryptophan Metabolism: The Rotterdam Periconceptional Cohort (Predict Study).

Background: The vital role of the maternal tryptophan (TRP) metabolism in maternal health and pregnancy is well established. However, non-medical maternal determinants influencing the TRP metabolism have been poorly investigated. We hypothesise that periconceptional maternal non-medical determinants alter the TRP metabolism, affecting both kynurenine (KP) and serotonin pathway (SP) metabolite concentrations.

The fully automated Sysmex XN-31 hematology analyzer can detect bloodstream form Trypanosoma brucei.

Background: For fully automated detection and quantification of Plasmodium parasites, Sysmex developed the XN-31 hemocytometer. This study investigated whether the XN-31 can also detect and quantify bloodstream form trypanosomes (trypomastigotes).

Methods: Axenic cultures of Trypanosoma brucei brucei were used to prepare two dilution series of trypomastigotes in the whole blood of a healthy donor, which were subsequently examined by the XN-31 as well as by microscopic examination of thin and thick blood films.

The Sixth European Society of Pharmacogenomics and Personalised Therapy Congress.

On 8-9 November 2022, the European Society of Pharmacogenomics and Personalised Therapy organized its sixth biennial congress, in Belgrade, Serbia (congress website: www.sspt.rs).

and polymorphisms: implications on postoperative acute, chronic and experimental pain after cardiac surgery.

Investigate the potential role of (mu-opioid receptor) and (catechol-O-methyltransferase enzyme) polymorphisms in postoperative acute, chronic and experimental thermal pain. A secondary analysis of 125 adult cardiac surgery patients that were randomized between fentanyl and remifentanil during surgery and genotyped. Patients in the fentanyl group with the high-pain sensitivity haplotype required less postoperative morphine compared with the average-pain sensitivity haplotype (19.

Effects of pharmacogenetic variants on vemurafenib-related toxicities in patients with melanoma.

The pharmacokinetics and pharmacodynamics of vemurafenib are characterized by a wide interpatient variability. Since multiple polymorphic enzymes and drug transporters are involved in vemurafenib pharmacokinetics, we studied associations of polymorphisms on vemurafenib-associated toxicities. Prospectively collected samples of 97 melanoma patients treated with vemurafenib alone (n = 62) or in combination with cobimetinib (n = 35) were genotyped for (3435C>T), (421C>A, 34G>A) and (, 15389C>T) polymorphisms.

4th ESPT Conference: pharmacogenomics and personalized medicine - research progress and clinical implementation.

The Fourth European Society of Pharmacogenomics and Personalized Therapy biennial conference was organized in collaboration with the Italian Society of Personalized Medicine (SIMeP) and was held at Benedictine Monastery of San Nicolò l'Arena in Catania, Sicily (Italy) on 4-7 October 2017. The congress addressed the research progress and clinical implementation in pharmacogenomics and personalized medicine. The Fourth European Society of Pharmacogenomics and Personalized Therapy congress brought together leading international scientists and healthcare professionals actively working in the fields of pharmacogenomics and personalized therapy.

Pharmacogenomics education in medical and pharmacy schools: conclusions of a global survey.

The need for pharmacogenomic education is becoming more and more urgent. Our aim was to evaluate the progress in pharmacogenomics education since then, and to put forward further recommendations. A survey was sent to 248 schools of medicine, pharmacy, nursing and health professions around the world.

genotype can help to predict effectiveness and safety during opioid treatment for chronic low back pain: results from a retrospective study in an Italian cohort.

Background: Opioids are widely used for chronic low back pain (CLBP); however, it is still unclear how to predict their effectiveness and safety. Codeine, tramadol and oxycodone are metabolized by CYP/CYP450 2D6 (CYP2D6), a highly polymorphic enzyme linked to allele-specific related differences in metabolic activity.

Purpose: genetic polymorphisms could potentially help to predict the effectiveness and safety of opioid-based drugs in clinical practice, especially in the treatment of CLBP.

CYP3A5 and ABCB1 polymorphisms in living donors do not impact clinical outcome after kidney transplantation.

Aim: To investigate the association between donor CYP3A5 and ABCB1 polymorphisms and tacrolimus (Tac)-induced nephrotoxicity and renal function in kidney transplant recipients.

Methods: The CYP3A5 6986A>G and ABCB1 3435C>T polymorphisms were determined in 237 recipients and donors.

Results: There was no significant association between Tac-related nephrotoxicity and donor CYP3A5 and ABCB1 genotype.

Detection of a rare CYP3A4 variant in a transplant patient characterized by a tacrolimus poor metabolizer phenotype.

A validated CYP3A genotype classification system allows clustering patients into poor, intermediate and extensive metabolizer phenotypes. However, substantial overlap exists between the clusters. A rare CYP3A4 allele, named CYP3A4*20 (rs67666821), has been specifically described in the Spanish population.

Advanced cancer pain: the search for genetic factors correlated with interindividual variability in opioid requirement.

Aim: To assess association between genetic variants and opioid requirement in cancer patients.

Materials & Methods: A prospective observational trial of 243 advanced cancer patients with inadequate analgesia treated by the palliative care team was analyzed for ABCB1, ARRB2, COMT, GCH1, IL1RN, KCNJ6, OPRM1, RHBDF2, SCN9A and Stat6 polymorphisms.

Results: For patients carrying OPRM1 118AG/GG and COMT 472GG (Val158Val) or these genotypes alone, a significant higher median percentage dose increase was observed (95.

Minimum information required for a DMET experiment reporting.

Aim: To provide pharmacogenomics reporting guidelines, the information and tools required for reporting to public omic databases.

Material & Methods: For effective DMET data interpretation, sharing, interoperability, reproducibility and reporting, we propose the Minimum Information required for a DMET Experiment (MIDE) reporting.

Results: MIDE provides reporting guidelines and describes the information required for reporting, data storage and data sharing in the form of XML.

Polymorphisms in SLCO1B1 and UGT1A1 are associated with sorafenib-induced toxicity.

Aim: Sorafenib-treated patients display a substantial variation in the incidence of toxicity. We aimed to investigate the association of genetic polymorphisms with observed toxicity on sorafenib.

Patients & Methods: We genotyped 114 patients that were treated with sorafenib at the Erasmus MC Cancer Institute, the Netherlands, for SLCO1B1, SLCO1B3, ABCC2, ABCG2, UGT1A1 and UGT1A9.

Pharmacokinetic drug-drug interaction study between raltegravir and citalopram.

Background: Depression is the most common mental health disorder among HIV-infected patients. When treating HIV-infected patients with a selective serotonin reuptake inhibitor (SSRI), potential drug-drug interactions with antiretroviral agents have to be taken into account. We investigated the two-way pharmacokinetic drug-drug interaction and tolerability of concomitant administration of the SSRI citalopram and the HIV-1 integrase inhibitor raltegravir in healthy volunteers.

Conference scene: pharmacogenomics: from cell to clinic (part 2).

Second International ESPT Meeting Lisbon, Portugal, 26-28 September 2013 The second European Society of Pharmacogenomics and Theranostics (ESPT) conference was organized in Lisbon, Portugal, and attracted 250 participants from 37 different countries. The participants could listen to 50 oral presentations, participate in five lunch symposia and were able to view 83 posters and an exhibition. Part 1 of this Conference Scene was presented in the previous issue of Pharmacogenomics.

Genetic variation in the PPARA gene is associated with simvastatin-mediated cholesterol reduction in the Rotterdam Study.

Aim: Recently, minor alleles of two strongly linked polymorphisms in the PPARA gene, rs4253728 G>A and rs4823613 A>G, were related to decreased CYP3A4 expression and activity. We studied whether they were associated with the cholesterol-lowering effect of simvastatin.

Materials & Methods: We identified 123 incident users with cholesterol measurements before and after starting statin therapy in a prospective population-based cohort study.

CYP3A4*22 and CYP3A combined genotypes both correlate with tacrolimus disposition in pediatric heart transplant recipients.

Background: Tacrolimus metabolism depends on CYP3A4 and CYP3A5. We aimed to determine the relationship between the CYP3A4*22 polymorphism and combined CYP3A genotypes with tacrolimus disposition in pediatric heart transplant recipients.

Methods: Sixty pediatric heart transplant recipients were included.

Consequences of the 118A>G polymorphism in the OPRM1 gene: translation from bench to bedside?

The 118A>G single nucleotide polymorphism (SNP) in the μ-opioid receptor (OPRM1) gene has been the most described variant in pharmacogenetic studies regarding opioid drugs. Despite evidence for an altered biological function encoded by this variant, this knowledge is not yet utilized clinically. The aim of the present review was to collect and discuss the available information on the 118A>G SNP in the OPRM1 gene, at the molecular level and in its clinical manifestations.

Clinical Application of Pharmacogenetics: Where are We Now?

Pharmacogenetic (PGx) testing has the potential to improve drug therapy in an individual by informing appropriate drug dosing or drug selection in order to maximize efficacy and safety. Although multiple studies have illustrated the potential benefits of such testing when applied to specific drugs across a broad range of therapy areas, the uptake of PGx testing in routine clinical practice has been relatively limited. Implementation appears to be hampered by the absence of sufficiently strong evidence linking the results of testing with actionable benefits in terms of clinical outcomes.

Practical recommendations for pharmacogenomics-based prescription: 2010 ESF-UB Conference on Pharmacogenetics and Pharmacogenomics.

The present article summarizes the discussions of the 3rd European Science Foundation-University of Barcelona (ESF-UB) Conference in Biomedicine on Pharmacogenetics and Pharmacogenomics, which was held in June 2010 in Spain. It was focused on practical applications in routine medical practice. We provide practical recommendations for ten different clinical situations, that have either been approved or not approved by regulatory agencies.

The pharmacogenetics of calcineurin inhibitors: one step closer toward individualized immunosuppression?

The immunosuppressive drugs cyclosporin (CsA) and tacrolimus (Tac) are widely used to prevent acute rejection following solid-organ transplantation. However, the clinical use of these agents is complicated by their many side effects, a narrow therapeutic index and highly variable pharmacokinetics. The variability in CsA and Tac disposition has been attributed to interindividual differences in the expression of the metabolizing enzymes cytochrome P450 (CYP) 3A4 and 3A5, and in the expression of the drug transporter P-glycoprotein (encoded by the ABCB1 gene, formerly known as the multidrug resistance 1 gene).