Pharmacogenomic testing identifies gene polymorphisms impacting drug metabolism, aiding in optimizing treatment efficacy and minimizing toxicity, thus potentially reducing healthcare utilization. 6-Mercaptopurine metabolism is affected by thiopurine methyltransferase ( TPMT ) and nudix hydrolase 15 ( NUDT15 ) polymorphisms. We sought to estimate the budget impact of preemptive pharmacogenomic testing for these genes in pediatric acute lymphoblastic leukemia (ALL) patients from an institutional perspective.

Pharmacogenomic testing can optimize drug efficacy and minimize adverse effects. CYP3A5 polymorphisms affect the metabolism of tacrolimus. We sought to estimate the budget impact of preemptive pharmacogenomic testing for CYP3A5 in pediatric heart transplantation patients from an institutional perspective.

We aimed to classify genetic variants in RYR1 and CACNA1S associated with malignant hyperthermia using biobank genotyping data in patients exposed to triggering anesthetics without malignant hyperthermia phenotype.

Genetic polymorphisms have been associated with risk of antituberculosis treatment toxicity. We characterized associations with adverse events and treatment failure/recurrence among adults treated for tuberculosis in Brazil.

Pharmacogenetics promises to optimize treatment-related outcomes by informing optimal drug selection and dosing based on an individual's genotype in conjunction with other important clinical factors. Despite significant evidence of genetic associations with drug response, pharmacogenetic testing has not been widely implemented into clinical practice. Among the barriers to broad implementation are limited guidance for how to successfully integrate testing into clinical workflows and limited data on outcomes with pharmacogenetic implementation in clinical practice. The Pharmacogenomics Global Research Network Implementation Working Group seeks to engage institutions globally that have implemented pharmacogenetic testing into clinical practice or are in the process or planning stages of implementing testing to collectively disseminate data on implementation strategies, metrics, and health-related outcomes with the use of genotype-guided drug therapy to ultimately help advance pharmacogenetic implementation. This paper describes the goals, structure, and initial projects of the group in addition to implementation priorities across sites and future collaborative opportunities.

Ibrutinib treatment is often complicated by cardiovascular side effects (CVSEs). The objective of this retrospective pharmacogenetic study is to replicate a previously reported association of 'high-risk' patients, who are homozygous carriers of at least two of GATA4 rs804280 AA, KCNQ1 rs163182 GG, and KCNQ1 rs2237895 AA, with increased risk of hypertension or atrial fibrillation, and explore associations for other pharmacogenes (e.g. CYP3A4, CYP3A5, CYP2D6, and ABCB1) with ibrutinib CVSEs. Univariate associations with P < 0.05 were adjusted for significant pretreatment cardiovascular conditions. In total 57 patients were included in the analysis. In the primary analysis, 'high-risk' patients were not more likely to experience hypertension or atrial fibrillation (70 vs. 41%, chi-square P value = 0.06). In secondary analyses, 'high-risk' patients were more likely to experience any CVSE during treatment (75 vs. 41%, P = 0.013), develop a cardiac rhythm or function disorder (65 vs. 24%, P = 0.008), and have a treatment modification due to CVSE (45 vs. 8%, P = 0.004). Additionally, high-risk homozygous variant genotypes of KCNQ1 rs163182 GG and rs2237895 AA were each associated with an increased likelihood of treatment modifications due to CVSE (40 vs. 11%, P = 0.021 and 45 vs. 9%, P = 0.004, respectively) and cardiac rhythm or function disorders (60 vs. 27%, P = 0.037 and 60 vs. 27%, P = 0.037). This study found supportive evidence that 'high-risk' genotype was associated with increased ibrutinib CVSEs. Validation of these associations is necessary before prospective trials testing whether personalized ibrutinib treatment approaches improve clinical outcomes.

Drug-induced long QT syndrome (diLQTS) is an adverse reaction from over 150 FDA-approved medications, posing the risk of triggering torsades de pointes and sudden death. While common genetic variants may modestly impact QT interval individually, their collective effect can significantly amplify risk of diLQTS. Consequently, this study aimed to validate a polygenic risk score (PRS) for diLQTS previously proposed by Strauss et al .

The research question is as follows: Are estrogen and progesterone receptor genotypes associated with thin endometrium? We performed a prospective cohort study of 129 patients who underwent preimplantation genetic testing for aneuploidies. These patients were categorized according to endometrial thickness: >7 mm control group (n = 94) and ≤7 mm study group (n = 35). Polymorphisms in the genes ESR1 (rs9340799 and rs3138774), ESR2 (rs1256049 and rs4986938), and PGR (rs1042838) were analyzed. Regarding genotype distribution, the GA/AA genotype frequency for rs4986938-ESR2 was higher in the thin endometrium group (80% in the study group vs. 50% in the control group; P = 0.002), as well as the GG genotype of PGR (8.6% in the study group vs. 0% in the control group; P = 0.002). No differences were observed for the remaining genotypes. In terms of clinical data, the pregnancy rate after euploid embryo transfer was lower in patients with the AA genotype for rs4986938-ESR2 (18.2% AA vs. 40.8% GA vs. 44.0% GG; P = 0.039). Finally, a predictive pregnancy model was developed using clinical data and ESR2 and PGR genotypes, with an area under the curve of 0.76, sensitivity of 64%, and specificity of 76%. The genetic variants rs4986938 in the ESR2 gene and rs1042838 in the PGR gene seem to correlate with idiopathic thin endometrium. In addition, the rs4986938 polymorphism in the ESR2 gene is associated with pregnancy rate. Finally, a predictive model combining clinical data and patient genetic profiles has been proposed to predict clinical pregnancy outcomes.

Heterocyclic amines (HCAs) are mutagens and carcinogens primarily generated when cooking meat at high temperatures or until well-done, and their major metabolic pathway includes hepatic N-hydroxylation via CYP1A2 followed by O-acetylation via N-acetyltransferase 2 (NAT2). NAT2 expresses a well-defined genetic polymorphism in humans resulting in rapid and slow acetylators. Recent epidemiological studies reported significant associations between dietary HCA exposure and insulin resistance and type II diabetes.

We report, for the first time, the distribution of four no-function NAT2 single nucleotide polymorphisms and inferred NAT2 acetylator phenotypes in three indigenous groups (Munduruku, Paiter-Suruí, and Yanomami), living in reservation areas in the Brazilian Amazon.

To investigate the association of CYP2C9 metabolic phenotypes with phenytoin plasma concentration ([PTH]) in neurosurgical patients from the Brazilian Public Health System.

Warfarin has a narrow therapeutic window and large variability in dosing that are affected by clinical and genetic factors. To help guide the dosing of warfarin, the Clinical Pharmacogenetics Implementation Consortium has recommended the use of pharmacogenetic algorithms, such as the ones developed by the International Warfarin Pharmacogenetics Consortium (IWPC) and by Gage et al. when genotype information is available.

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.

The incidence of lung adenocarcinoma (LAD) is increasing worldwide. Single-nucleotide polymorphisms in aldehyde dehydrogenase 2 family member gene ( ALDH2 ) rs671 and alcohol dehydrogenase 1B ( ADH1B ) rs1229984 are common and functionally important genetic variants to metabolize endogenous and exogenous aldehyde chemicals, related to cancer.

Understanding the influence of fetal and maternal genetics on prenatal drug exposure could potentially improve benefit-risk evaluation. In this study, we investigated the impact of two functional polymorphisms in CYP2B6 on prenatal exposure to efavirenz.

The purpose of this study was to evaluate the effect of UGT1A4 and UGT2B7 polymorphisms on the plasma concentration of lamotrigine in Chinese patients with bipolar disorder.

Based on driver mutations and gene expression profiles, the International Consensus Classification currently divided the entity 'Philadelphia chromosome-positive (Ph+) B-cell precursor acute lymphoblastic leukemia (ALL)' into two subtypes: lymphoid-only and multilineage involvement (Ph+ ALL-L and -M, respectively). The similar biological characteristics of Ph-like ALL and Ph+ ALL drove us to assume that Ph-like ALL-M subtypes exist. This report presents two pediatric ALL cases (one Ph+ and one Ph-like) with minimal residual disease negativity established by multicolor flow cytometry but persistent transcript detection by quantitative PCR (qPCR) even after second-line treatment with tyrosine kinase inhibitors combined with blinatumomab immunotherapy. Using droplet digital PCR, BCR::ABL1 or TPM3::PDGFRB transcripts were identified in CD19+ cells as well as in non-CD19+ cells, suggesting the presence of a Ph+ or Ph-like ALL-M subtype originating from hematopoietic stem cells. This report provides information for better characterization, diagnosis, and treatment of these ALL subtypes.

This study aims to understand patient and healthcare provider perspectives on the integration and application of pharmacogenetics (PGx) testing in routine clinical practice.

It is unclear whether renal transplant recipients treated with mycophenolic acid (MPA) who carry the reduced-function allele at polymorphism SLCO1B1 c.521T>C differ from their wild-type peers regarding renal outcomes and tolerability. We aimed to estimate the effect of this polymorphism on the graft function (estimated glomerular filtration rate, eGFR) over the first 12 post-transplant months in patients on MPA-based maintenance immunosuppression.

The CYP2D6 enzyme is crucial for the metabolism and disposition of a variety of drugs. This study was conducted to examine the relationship between CYP2D6 gene polymorphisms and the response to angiotensin receptor blocker (ARB)-based treatment in patients of Chinese Bai ethnicity with hypertension.