Pharmacogenomic testing is rapidly becoming the standard of care in treating pediatric acute lymphoblastic leukemia (ALL). Risk classification of ALL can be performed through whole transcriptome sequencing (WTS) of diagnostic tumor samples. We evaluated the feasibility of inferring germline pharmacogenomic genotypes from the tumor transcriptome in ALL.

In Canada, access to pharmacogenetic (PGx) testing remains limited, particularly outside of research institutions, and commercial testing is often cost-prohibitive. To address access challenges, several Canadian insurance providers have begun offering PGx test coverage; however, the extent and nature of this coverage remain unclear. This study systematically reviewed publicly available PGx coverage policies from Canadian insurance companies to evaluate eligibility requirements, affiliated laboratories, and clinical actionability of test panels. Ten Canadian insurers were identified with publicly accessible PGx testing policies. Six offered partial reimbursement or discounted pricing to all members, while four restricted full coverage to individuals meeting specific criteria, such as being on disability leave or having a physician's diagnosis. Eligibility requirements varied considerably, with some insurers requiring multiple conditions to be met. Four commercial laboratories were affiliated with insurers, but these labs differed substantially in the number of actionable genes and drugs tested. Our findings highlight substantial heterogeneity in insurer eligibility criteria and affiliate lab test comprehensiveness that may create inequities in access and quality of care. Furthermore, variability in insurance coverage may influence clinicians' willingness to recommend testing and patients' ability to access personalized therapy. These findings underscore the need for standardized PGx testing coverage policies and harmonized testing panels. Collaboration among insurers, researchers, and clinicians is essential to generating Canadian-specific evidence to guide equitable and clinically effective PGx implementation.

Large consortia link variants in SLC22A1 , SLC47A1 , and GLP1R to antidiabetic response, yet few data confirm these effects in small real-world cohorts. We tested whether three common polymorphisms translate into measurable 3-month metabolic changes.

Dyslipidemia is a crucial risk factor for atherosclerotic cardiovascular disease. Although rosuvastatin is widely used, treatment response varies significantly due to genetic variation. This study investigated the pharmacogenomic impact of low-density lipoprotein receptor (LDLR) 3' untranslated region (UTR) variants on rosuvastatin efficacy in a Chinese Han adult cohort with dyslipidemia.

Dehydroepiandrosterone (DHEA) is considered an endogenous steroid hormone precursor, and 17-ß estradiol (E2) is one of the estrogen steroid hormones. Of the 13 known human cytosolic sulfotransferases (SULTs), SULT2B1a has been shown to be expressed in steroid hormone-responsive tissues such as the prostate, ovary, and placenta, as well as the fetal brain. Previous studies have demonstrated that SULT2B1a is capable of sulfating 3β-hydroxysteroids such as DHEA and pregnenolone. The present study aimed to investigate the effects of human SULT2B1 single-nucleotide polymorphisms (SNPs) on the enzymatic characteristics of SULT2B1a allozymes in mediating the sulfation of DHEA and E2.

The pathogenic mechanisms of antituberculosis drug-induced liver injury (AT-DILI) remain unclear. Isoniazid and rifampicin may lead to hepatic accumulation of protoporphyrin IX in which heme synthesis ferrochelatase (FECH), a key rate-limiting enzyme, potentially plays an important role. This study aimed to investigate the combined effects of FECH gene polymorphisms and promoter methylation on AT-DILI risk in the Eastern Chinese population.

Pharmacogenetic testing plays a key role in personalized pharmacotherapy and improving treatment outcomes; however, its benefit in clinical hyperpolypharmacy (≥ 10 chronic drugs) remains uncertain.

Irinotecan treatment is often complicated by gastrointestinal, hematological, and infusion-related toxicities, the latter of which typically presents as acute cholinergic syndrome (ACS). While genetic variation in UGT1A1 increases toxicity risk, fewer studies have investigated variation in other genes. This study aimed to assess the impact of variation in other genes involved in irinotecan pharmacokinetics with irinotecan-related toxicity. This was a retrospective study of patients receiving standard irinotecan doses (180 mg/m2) with available genetic and clinical data. The primary analysis was to investigate the impact of carboxylesterase (CES) genetic variation on irinotecan infusion-related ACS. Exploratory secondary analyses evaluated variation in CES1, CES2, UGT1A7, UGT1A9, ABCB1, ABCG2, ABCC2, and SLCO1B1 with severe toxicity, treatment modification, diarrhea, and neutropenia. Univariate associations with P less than 0.05 were adjusted for UGT1A1*28 and UGT1A1*6 genotype. A total of 93 patients were included in this analysis. CES1 variants were not associated with infusion-related ACS. In the exploratory analysis, CES1 rs3785161 AA was associated with an increased likelihood of severe irinotecan toxicity (37 vs. 16%; P = 0.034), and ABCG2 rs2231142 AA/AC was associated with an increased likelihood of severe neutropenia (33 vs. 8%; P = 0.017). CES1 and ABCG2 variants may increase the risk of irinotecan toxicity. Further studies are needed to validate these associations to justify prospective studies investigating the clinical benefits of genetics-guided irinotecan dosing.

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with poor prognosis, shaped by both environmental and genetic factors. While genome-wide association studies have identified several IPF risk loci, the genetic basis remains incomplete, especially in non-European populations.

It is unknown how many people in the US have had pharmacogenetic (PGx) testing and whether people want to be tested. We conducted a nationally representative survey of the general US adult population to determine the prevalence of adults that have had PGx testing using a validated confidential online survey, the Non-Medical Use of Prescription Drugs Program. A weighted logistic regression was used to test health characteristics associated with PGx testing and determine those who desire to be tested. The analysis included 29 146 individuals who completed the survey, which represents approximately 260 000 000 adults in the US. The prevalence of US adults who have been PGx tested is 6.6% [95% confidence interval (CI): 6.2-7.0]. Only 32.2% (95% CI: 31.5-32.9), an estimated 79 million individuals, desired PGx testing. Adults who had or want PGx testing were more likely to be female, have higher education, be students, current or former members of the military, use medications, and have a mental health disorder. The prevalence of adults who have been PGx tested remains low in the US. There are knowledge gaps about the benefits of PGx testing that must be bridged to increase implementation.

Warfarin is a commonly used oral anticoagulant for managing thromboembolic events after cardiac valve surgery. However, its optimal dose varies between individuals, often requiring trial and error to determine. This study aimed to investigate the association of polymorphisms in the CYP2C9 and VKORC1 genes with warfarin dose requirements in an Iranian population undergoing cardiac valve replacement.

Praziquantel (PZQ) is commonly used to treat schistosomiasis; however, there is considerable interindividual variability in its efficacy, partly because of genetic variation. Data on this relationship is scarce across Africa - where schistosomiasis is prevalent. This study aimed to investigate the pharmacokinetic/pharmacodynamic and pharmacogenetic relationship between PZQ and its metabolites in a Zimbabwean population infected with Schistosoma haematobium by leveraging dried blood spots (DBS) and mass spectrometry (MS).

Evaluate the feasibility of implementing a multigene pharmacogenetic (PGx) test and genotype-guided pharmacist recommendations into gynecologic perioperative workflows and fidelity to pharmacist genotype-guided postoperative analgesic recommendations.

Propofol is commonly used to sedate patients, but variations in how individuals metabolize the drug may affect dosing requirements. The objective of this study was to explore how genetic variations in CYP450 enzymes, particularly CYP2B6 , influence propofol metabolism in ICU patients receiving mechanical ventilation. Genetic variants of CYP2B6 , CYP2C9 , CYP2C19 , and CYP3A5 were collected from an institutional genetic data repository. Patients were dichotomized into low and high metabolic activity for each enzyme, and the mean weight- and time-normalized propofol dose administered was compared between groups via t test. There was no significant difference in average daily propofol dose between patients with low and high CYP2B6 activity (11 vs. 11 mg/kg/h, P  = 0.78), or any of the other CYP enzymes analyzed (all P  > 0.05). This study could not replicate previous studies indicating that patients carrying genetic variants with diminished CYP2B6 activity required lower propofol doses. Future studies with prospectively collected dosing and outcomes data, and measurement of plasma drug concentrations, may provide insights into personalized propofol dosing strategies.

RASopathies are rare genetic disorders caused by germline mutations in genes that regulate the RAS-mitogen-activated protein kinase (MAPK) pathway, a critical pathway involved in various cellular processes. Disruption of this pathway leads to multisystemic manifestations, including cardiomyopathies, a cause of high morbi-mortality. In response to the urgent need to improve survival in patients with RASopathies, alternative therapies, such as MAPK inhibitors traditionally used in cancer treatment, have been explored. This article reviews the current evidence on the use of these medications in treating cardiomyopathies associated with RASopathies. The search was conducted in the PubMed, Scopus, and Embase databases identifying nine studies reporting a total of 14 cases (nine with Noonan syndrome and five with Costello syndrome) where patients were successfully treated with trametinib, a MEK inhibitor. This therapeutic alternative broadens the horizons of opportunity for patients who often face limited options for enhancing their quality of life. Therefore, it is important to prioritize ongoing research in this field, focusing not only on further investigation on trametinib, but also exploring other potential therapeutic approaches.

Optimizing antiplatelet therapy is crucial in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary interventions (PCIs). This study aimed to assess the prevalence of CYP2C19 loss-of-function (LOF) variants and evaluate the clinical outcome of ticagrelor, clopidogrel, and aspirin in patients with ACS-PCI.

To explore the distribution of clinically relevant UGT1A1 polymorphisms and inferred UGT1A1 phenotypes in two Indigenous groups (Paiter-Suruí and Yanomami) from reservation areas in the Brazilian Amazon.

Regulatory T (Treg) cell depletion-associated immune tolerance deficiency have been shown to play a key role in the pathogenesis of primary Sjögren's syndrome (pSS). Treg cells mainly express the transcriptional regulator Foxp3 and are characterized by constitutively high expression of inhibitory coreceptor CTLA-4 . Herein, the aim of this study was to investigate the potential association of single nucleotide polymorphisms (SNPs) in Foxp3 and CTLA-4 genes with the susceptibility to pSS.

This short communication serves as an update to previously published pilot study results on bronchodilator response (BDR) in children with asthma. We expanded our cohort from 54 to 165 pediatric patients seeking emergency department care for an asthma exacerbation. We obtained measured BDR before and after albuterol administration using the Pediatric Asthma Severity Score and collected genomic DNA. Based on a literature review, we analyzed whether 21 candidate single-nucleotide polymorphisms (SNPs) were associated with BDR. Among the three SNPs initially reported in our pilot study as significantly associated with BDR (rs912142, rs7081864, and rs7903366), we confirmed that rs7081864 was still significantly associated with suboptimal BDR (odds ratio, 0.47; confidence interval, 0.24-0.92). If externally validated in broader studies, simple outpatient testing for that SNP variant could help guide pharmacologic therapy for acute asthma symptoms.