Pharmacogenetics and genomics最新文献

{"title":"Polygenic risk score for drug-induced long QT syndrome: independent validation in a real-world patient cohort.","authors":"Ana I Lopez-Medina, Alessandra M Campos-Staffico, Choudhary Anwar A Chahal, Juliet P Jacoby, Isabella Volkers, Omer Berenfeld, Jasmine A Luzum","doi":"10.1097/FPC.0000000000000548","DOIUrl":"10.1097/FPC.0000000000000548","url":null,"abstract":"<p><strong>Objective: </strong>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 .</p><p><strong>Methods: </strong>A retrospective cohort study was conducted utilizing patients from the Michigan Genomics Initiative prescribed 27 high-risk QT-prolonging drugs and an ECG during the prescription. The primary outcome was marked prolongation of the QTc interval (either >60 ms change from baseline or >500 ms absolute value) during treatment with a high-risk QT-prolonging drug.</p><p><strong>Results: </strong>The primary outcome occurred in 12.0% of n  = 6070 self-reported White, 12.4% of 558 African American, and 8.2% of 110 Asian patients. The PRS significantly associated with diLQTS in White patients [adjusted odds ratio = 1.44 (95% CI: 1.09-1.89); P  = 0.009]. However the study lacked sufficient statistical power to confirm the PRS as a risk factor in African Americans [adjusted odds ratio = 2.18 (95% CI: 0.98-5.49); P  = 0.073] and Asians [adjusted odds ratio = 3.21 (95% CI: 0.69-16.87); P  = 0.139] due to smaller sample sizes in these groups.</p><p><strong>Conclusion: </strong>The previously published PRS for diLQTS was validated in a large, real-world cohort, demonstrating its potential as a tool for identifying high-risk patients. Incorporating this PRS into routine clinical practice could enable proactive measures to prevent life-threatening diLQTS.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"45-56"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11543509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Pharmacogenomics Global Research Network Implementation Working Group: global collaboration to advance pharmacogenetic implementation.","authors":"Larisa H Cavallari, J Kevin Hicks, Jai N Patel, Amanda L Elchynski, D Max Smith, Salma A Bargal, Ashley Fleck, Christina L Aquilante, Shayna R Killam, Lauren Lemke, Taichi Ochi, Laura B Ramsey, Cyrine E Haidar, Teresa Ho, Nihal El Rouby, Andrew A Monte, Josiah D Allen, Amber L Beitelshees, Jeffrey R Bishop, Chad Bousman, Ronald Campbell, Emily J Cicali, Kelsey J Cook, Benjamin Duong, Evangelia Eirini Tsermpini, Sonya Tang Girdwood, David B Gregornik, Kristin N Grimsrud, Nathan Lamb, James C Lee, Rocio Ortiz Lopez, Tinashe Adrian Mazhindu, Sarah A Morris, Mohamed Nagy, Jenny Nguyen, Amy L Pasternak, Natasha Petry, Ron H N van Schaik, April Schultz, Todd C Skaar, Hana Al Alshaykh, James M Stevenson, Rachael M Stone, Nam K Tran, Sony Tuteja, Erica L Woodahl, Li-Chi Yuan, Craig R Lee","doi":"10.1097/FPC.0000000000000547","DOIUrl":"10.1097/FPC.0000000000000547","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"1-11"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Updated analysis of the pharmacogenomics of pediatric bronchodilator response.","authors":"Jennifer Brailsford, Guillaume Labilloy, Nolan Menze, Morgan Henson, Jennifer Fishe","doi":"10.1097/FPC.0000000000000557","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000557","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of ADH1B and ALDH2 genotypes with the risk of lung adenocarcinoma.","authors":"Tzu-Yu Pan, Jui-Ying Lee, Jia-Jen Chen, Yu-Wei Liu, A Nishawlini Abishaw, Ming-Wei Su, Chien-Wei Lin, Tusty-Jiuan Hsieh, Chiung-Yu Peng, Robert J Turesky, Medjda Bellamri, Aij-Lie Kwan, Chia-Fang Wu, Ming-Tsang Wu","doi":"10.1097/FPC.0000000000000555","DOIUrl":"10.1097/FPC.0000000000000555","url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>This is a case-control study. A total of 150 newly diagnosed LAD patients were from Kaohsiung Medical University Hospital, Taiwan, between 2019 and 2022. Two control groups, TWB-1 ( n  = 600) and TWB-2 ( n  = 29 683), were selected from Taiwan Biobank (TWB), and the case patients were frequency-matched with TWB-1 based on age category (30-60 or >60 years old), sex, and education levels. Logistic regression models were employed to analyze the association between two genetic variants and LAD risk.</p><p><strong>Results: </strong>A significant association was noted between ALDH2 and LAD risk. Those with ALDH2 rs671 *2/*2 in TWB-1 and TWB-2 controls had a 2.68-fold (95% CI = 1.43-4.99) and a 1.83-fold (95% CI = 1.07-3.11) increased risk of LAD, respectively, compared with those with ALDH2 rs671 *1/*1 or *1/*2 , after adjusting for covariates. This association was particularly pronounced in females. No overall significant association between ADH1B rs1229984 and LAD risk was observed.</p><p><strong>Conclusion: </strong>The findings indicate a strong and robust risk association between ALDH2 rs671*2/*2 and LAD in the Taiwan population, particularly in Taiwanese female adults.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential distribution of NAT2 polymorphisms and NAT2 acetylator phenotypes among indigenous populations of the Brazilian Amazon.","authors":"Jamila A Perini, Paulo C Basta, Jessica V Cardoso, Anna Beatriz R Elias, Guilherme Suarez-Kurtz","doi":"10.1097/FPC.0000000000000544","DOIUrl":"10.1097/FPC.0000000000000544","url":null,"abstract":"<p><strong>Objectives: </strong>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.</p><p><strong>Methods: </strong>Two hundred and seventy-six participants from three indigenous groups (92 for each group) were included and genotyped for four NAT2 polymorphisms (rs1801279, rs1801280, rs1799930, and rs1799931) by the TaqMan system. Minor Allele Frequency (MAF) was determined and NAT2 acetylator phenotypes were inferred.</p><p><strong>Results: </strong>NAT2 rs1801279G>A was absent in all cohorts; rs1799930G>A was absent in Yanomami and rare (MAF 0.016) in Munduruku and Paiter-Suruí; MAF of rs1801280T>C ranged five-fold (0.092-0.433), and MAF of rs1799931G>A varied between 0.179 and 0.283, among the three groups. The distribution of NAT2 phenotypes differed significantly across cohorts; the prevalence of the slow acetylator phenotype ranged from 16.3% in Yanomami to 33.3% in Munduruku to 48.9% in Paiter-Suruí. This three-fold range of variation is of major clinical relevance because the NAT2 slow phenotype is associated with higher risk of hepatotoxicity with antituberculosis chemotherapy and high incidence rates of tuberculosis and burden of latent infection among Munduruku, Paiter-Surui, and Yanomami peoples. According to the frequency of the NAT2 slow acetylator phenotype, the estimated number of individuals needed to be genotyped to prevent one additional event of hepatotoxicity range from 31 (Munduruku) to 39 (Paiter-Surui) and to 67 (Yanomami).</p><p><strong>Conclusion: </strong>The rs1801279 polymorphism was not found in any of the cohorts, while the MAF of the other polymorphisms showed significant variation between the cohorts. The difference in the prevalence of the NAT2 slow acetylator phenotype, which is linked to isoniazid-induced hepatotoxicity, was observed in the different study cohorts.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"269-274"},"PeriodicalIF":1.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative performance of pharmacogenetics-based warfarin dosing algorithms in Chinese population: use of a pharmacokinetic/pharmacodynamic model to explore dosing regimen through clinical trial simulation.","authors":"Keli Shi, Jiexin Deng","doi":"10.1097/FPC.0000000000000545","DOIUrl":"10.1097/FPC.0000000000000545","url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>In this study, simulations were performed in Chinese cohorts to explore how dosing differences between Western (by IWPC and Gage et al.) and Chinese algorithms (by Miao et al.) would mean in terms of anticoagulation effect in clinical trials. We first tried to replicate a published clinical trial comparing genotype-guided dosing to routine clinical dosing in Chinese patients. We then made simulations where Chinese cohorts received daily doses recommended by Gage, IWPC, and Miao algorithms.</p><p><strong>Results: </strong>We found that in simulation conditions where dosing specifications were strictly followed, genotype-guided dosing by IWPC and Lenzini formulae was more likely to overshoot the upper limit of the therapeutic window by day 15, and thus may have a lower % time in therapeutic range (%TTR) than that of clinical dosing group. Also, in comparing Gage, IWPC, and Miao algorithms, we found that the Miao dosing cohort has the highest %TTR and the lowest risk of over-anticoagulation by day 28.</p><p><strong>Conclusion: </strong>In summary, our results confirmed that algorithms developed based on data from local patients may be more suitable for achieving therapeutic international normalized ratio window in Chinese population.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"34 9","pages":"275-284"},"PeriodicalIF":1.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11424055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of CYP2C9 phenotypes on phenytoin plasma concentration in neurosurgical Brazilian patients.","authors":"Pedro Kurtz, Anna Beatriz Ribeiro Elias, Guilherme Suarez-Kurtz","doi":"10.1097/FPC.0000000000000546","DOIUrl":"10.1097/FPC.0000000000000546","url":null,"abstract":"<p><strong>Aims: </strong>To investigate the association of CYP2C9 metabolic phenotypes with phenytoin plasma concentration ([PTH]) in neurosurgical patients from the Brazilian Public Health System.</p><p><strong>Methods: </strong>Patients (n = 170) were treated with phenytoin (300 mg/day) perioperatively as prophylaxis for postoperative seizures. Two to 10 days after surgery, a blood sample was collected for quantification of [PTH] and genotyping of CYP2C9*2 and *3 alleles. CYP2C9 metabolic phenotypes, NM (normal), IM (intermediate), and PM (poor) metabolizer, were inferred from CYP2C9 diplotypes. Linear regression modeling was applied to identify predictors of [PTH].</p><p><strong>Results: </strong>Wide (22-fold) interindividual variation in [PTH] was observed (2.2-47.5 mg/l). [PTH] associated significantly (Kruskal-Wallis P < 0.005) with CYP2C9 phenotypes and there was a significant trend (Jonckheere-Terpstra test, P < 0.0001) for [PTH] increase in the order NM < IM < PM. [PTH] was within the target therapeutic range (10-20 mg/l) in 34.7% of patients, while 39.4% and 25.9% had [PTH] below and above the range, respectively. CYP2C9 phenotypes associated significantly (chi-square P = 0.004) with the distribution of patients in [PHT] therapeutic categories and the Cramér's V test pointed to moderate magnitude of the effect of CYP2C9 phenotypes (V = 0.211).</p><p><strong>Conclusion: </strong>Diplotype-predicted CYP2C9 metabolic phenotypes are associated significantly with [PTH] in neurosurgical Brazilian patients receiving phenytoin for postsurgery seizure prophylaxis. [PHT] increased progressively in the phenotype order NM < IM < PM, and all PM patients had [PHT] above the target therapeutic range, consistent with the CPIC guideline 'strong' recommendation for phenytoin dosing adjustments in PMs.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"34 9","pages":"285-290"},"PeriodicalIF":1.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CYP3A5 pharmacogenetic testing for tacrolimus in pediatric heart transplant patients: a budget impact analysis.","authors":"Jiaqi Wang, Amy L Pasternak, Simran Maggo, Rochelle Mindanao, Jenny Q Nguyen, Cynthia L Gong","doi":"10.1097/FPC.0000000000000549","DOIUrl":"10.1097/FPC.0000000000000549","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>A decision tree was constructed to estimate the budget impact of pediatric heart transplant patients (age ≤18 years) initiated on tacrolimus with and without CYP3A5 pharmacogenomic testing. The budget impact of preemptive pharmacogenomic testing versus no pharmacogenomic testing was calculated. One-way sensitivity analysis and alternative analyses were conducted to assess the robustness of results to changes in model parameters.</p><p><strong>Results: </strong>CYP3A5 genotype-guided dosing provided savings of up to $17 225 per patient compared to standard dosing. These savings decreased to $11 759 when using another institution's data for the standard-dosing group. The time to achieve therapeutic concentration in the poor metabolizer genotype-guided dosing group had the largest impact on cost savings while the cost of the pharmacogenetic test had the smallest impact on cost savings.</p><p><strong>Conclusion: </strong>Implementing CYP3A5 testing could save $17 225 per pediatric heart transplant patient receiving tacrolimus. As pharmacogenomic testing becomes more widespread, institutions should track resource requirements and outcomes to determine the best implementation policies going forward.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Philadelphia chromosome-positive or Philadelphia chromosome-like B-cell precursor acute lymphoblastic leukemia with multilineage involvement in pediatric patients: a report of two cases and literature review.","authors":"Han Lin, Lu Chen, Ruoyao Huang, Shufang Xue, Gaoyuan Sun, Chengyi Wang, Shuhong Shen, Hui Zhang, Yongzhi Zheng","doi":"10.1097/FPC.0000000000000554","DOIUrl":"10.1097/FPC.0000000000000554","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Budget impact analysis of TPMT and NUDT15 pharmacogenomic testing for 6-mercaptopurine in pediatric acute lymphoblastic leukemia patients.","authors":"Beverly Fuerte, Mia Burgos, Vyvy Cao, Simran Maggo, Deepa Bhojwani, Teresa Rushing, Jenny Q Nguyen, Cynthia L Gong","doi":"10.1097/FPC.0000000000000550","DOIUrl":"10.1097/FPC.0000000000000550","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>A Markov model was constructed to model the first cycle of the maintenance phase of chemotherapy for pediatric ALL patients transitioning between one of three health states: stable, moderately myelosuppressed, and severely myelosuppressed over 16 weeks, with each health state's associated costs derived from the literature. The patient's likelihood to experience moderate or severe myelosuppression based on metabolism phenotype was calculated from the literature and applied on a weekly basis, and the marginal budget impact of preemptive pharmacogenomic testing vs. no pharmacogenomic testing was calculated. One-way sensitivity analysis was conducted to assess parameter influence on results.</p><p><strong>Results: </strong>Preemptive pharmacogenomic testing of TPMT and NUDT15 provided savings of up to $26 028 per patient during the maintenance phase. In the sensitivity analysis, the cost of outpatient management of moderate myelosuppression had the greatest impact on the budget, resulting in cost savings ranging from $8592 to $30 129 when the minimum and maximum costs of management were used in the model.</p><p><strong>Conclusion: </strong>Preemptive pharmacogenomic testing for TPMT and NUDT15 polymorphisms before initiation of maintenance therapy for pediatric ALL patients yielded considerable cost savings.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}