Pharmacogenetics and genomics最新文献

{"title":"Evaluation of tagged SNPs for HLA markers, HLA-B*15:02 and HLA-A*31:01, that are used to predict carbamazepine induced adverse effects: Erratum.","authors":"","doi":"10.1097/FPC.0000000000000556","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000556","url":null,"abstract":"","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"35 2","pages":"87"},"PeriodicalIF":1.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915482","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":"Pharmacogenetics of tuberculosis treatment toxicity and effectiveness in a large Brazilian cohort.","authors":"Gustavo Amorim, James Jaworski, Jing Yang, Marcelo Cordeiro-Santos, Afrânio L Kritski, Marina C Figueiredo, Megan Turner, Bruno B Andrade, Digna R Velez Edwards, Adalberto R Santos, Valeria C Rolla, Timothy R Sterling, David W Haas","doi":"10.1097/FPC.0000000000000552","DOIUrl":"10.1097/FPC.0000000000000552","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>Participants were followed in Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil. We included persons with culture-confirmed drug-susceptible pulmonary tuberculosis who started treatment between 2015 and 2019, and who were eligible for pharmacogenetics. Treatment included 2 months of isoniazid, rifampin or rifabutin, pyrazinamide, and ethambutol, then 4 months of isoniazid and rifampin or rifabutin, with 24-month follow-up. Analyses included 43 polymorphisms in 20 genes related to antituberculosis drug hepatotoxicity or pharmacokinetics. Whole exome sequencing was done in a case-control toxicity subset.</p><p><strong>Results: </strong>Among 903 participants in multivariable genetic association analyses, NAT2 slow acetylator status was associated with increased risk of treatment-related grade 2 or greater adverse events, including hepatotoxicity. Treatment failure/recurrence was more likely among NAT2 rapid acetylators, but not statistically significant at the 5% level. A GSTM1 polymorphism (rs412543) was associated with increased risk of treatment-related adverse events, including hepatotoxicity. SLCO1B1 polymorphisms were associated with increased risk of treatment-related hepatoxicity and treatment failure/recurrence. Polymorphisms in NR1/2 were associated with decreased risk of adverse events and increased risk of failure/recurrence. In whole exome sequencing, hepatotoxicity was associated with a polymorphism in VTI1A , and the genes METTL17 and PRSS57 , but none achieved genome-wide significance.</p><p><strong>Conclusion: </strong>In a clinical cohort representing three regions of Brazil, NAT2 acetylator status was associated with risk for treatment-related adverse events. Additional significant polymorphisms merit investigation in larger study populations, particularly regarding risk of treatment failure/recurrence.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"55-64"},"PeriodicalIF":1.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11695165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522633","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":"Metabolic effects of heterocyclic amines on insulin‑induced AKT phosphorylation and gluconeogenic gene expression are modified by N-acetyltransferase 2 genetic polymorphism.","authors":"Kennedy M Walls, Jonathan Y Joh, Madeline M Martinez, Kyung U Hong, David W Hein","doi":"10.1097/FPC.0000000000000559","DOIUrl":"10.1097/FPC.0000000000000559","url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>We assessed the effect of some of the most common HCAs found in cooked meat, 2-amino-3,4-dimethylimidazo[4,5-f]quinoline, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, on insulin signaling and gluconeogenic gene expression in cryopreserved human hepatocytes characterized by their NAT2 genotype and phenotype to investigate the role of NAT2 genetic polymorphism in HCA-induced metabolic dysregulation.</p><p><strong>Results: </strong>HCA treatment significantly reduced insulin-induced protein kinase B phosphorylation and significantly increased expression of genes involved in gluconeogenesis (G6PC, PCK1, FOXO1, and PPARA) in cryopreserved human hepatocytes from rapid but not from slow acetylators.</p><p><strong>Conclusion: </strong>The findings suggest that NAT2 genetic polymorphism modifies HCA-induced insulin resistance and gluconeogenic gene expression, implying that individuals with rapid acetylator phenotype may be at greater risk of dysregulated glucose homeostasis following exposure to HCAs.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060008","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 estrogen and progesterone receptor polymorphisms with idiopathic thin endometrium.","authors":"Belén Lledo, Mónica Hortal, María Martínez, Jose A Ortiz, Ruth Morales, Andrea Bernabeu","doi":"10.1097/FPC.0000000000000560","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000560","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060089","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":"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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664750/pdf/","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":"OA","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":"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":"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}