Pharmacogenetics and genomics最新文献

{"title":"Associations of CYP2C19 and F2R genetic polymorphisms with platelet reactivity in Chinese ischemic stroke patients receiving clopidogrel therapy.","authors":"Suli Zhang,&nbsp;Jinhang Zhu,&nbsp;Hua Li,&nbsp;Fengzhen Li,&nbsp;Bin Zhu,&nbsp;Tao Li,&nbsp;Shuxin Fang,&nbsp;Shengying Qin","doi":"10.1097/FPC.0000000000000462","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000462","url":null,"abstract":"<p><strong>Objectives: </strong>Genetic variation has been considered a major contributor to the high variability in the response to dual antiplatelet therapy in patients with acute ischemic stroke or transient ischemic attack. Recently, incidences of ischemic stroke are increasing rapidly in China. We aimed to evaluate the influence of potential determinants on the response of antiplatelet therapy and adverse events in Chinese ischemic stroke patients receiving clopidogrel-aspirin treatment.</p><p><strong>Methods: </strong>Based on the clopidogrel drug response pathway and the coagulation and anticoagulation function, we systematically selected 34 genetic polymorphisms in 12 candidate genes. Three hundred and eight patients were divided into 2 groups according to their degree of inhibition of platelet aggregation. Multivariate analysis was then performed to assess the influence of demographic, clinical and genetic factors on platelet reactivity in Chinese ischemic stroke patients.</p><p><strong>Results: </strong>We found that polymorphisms in CYP2C19 and F2R genes were still significantly associated with platelet reactivity in Chinese ischemic stroke patients (P = 0.037 and 0.015). The newly identified rs168753 in F2R gene may influence the efficacy to clopidogrel-aspirin therapy for ischemic stroke patients. We also found that ischemic stroke patients with low level of inhibition of platelet aggregation had higher risk of recurrent ischemic events (P = 0.001).</p><p><strong>Conclusions: </strong>Together, these results emphasized the necessity of genotype-directed antiplatelet therapy and facilitated to minimize adverse ischemic events.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"32 4","pages":"138-143"},"PeriodicalIF":2.6,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10543636","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":"Anesthesia providers as stakeholders to adoption of pharmacogenomic information in perioperative care.","authors":"Tien M Truong,&nbsp;Jeffrey L Apfelbaum,&nbsp;Emily Schierer,&nbsp;Keith Danahey,&nbsp;Brittany A Borden,&nbsp;Theodore Karrison,&nbsp;Sajid Shahul,&nbsp;Magdalena Anitescu,&nbsp;Rebecca Gerlach,&nbsp;Randall W Knoebel,&nbsp;David O Meltzer,&nbsp;Mark J Ratain,&nbsp;Peter H O'Donnell","doi":"10.1097/FPC.0000000000000455","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000455","url":null,"abstract":"<p><strong>Objectives: </strong>Integration of pharmacogenomics into clinical care is being studied in multiple disciplines. We hypothesized that understanding attitudes and perceptions of anesthesiologists, critical care and pain medicine providers would uncover unique considerations for future implementation within perioperative care.</p><p><strong>Methods: </strong>A survey (multiple choice and Likert-scale) was administered to providers within our Department of Anesthesia and Critical Care prior to initiation of a department-wide prospective pharmacogenomics implementation program. The survey addressed knowledge, perceptions, experiences, resources and barriers.</p><p><strong>Results: </strong>Of 153 providers contacted, 149 (97%) completed the survey. Almost all providers (92%) said that genetic results influence drug therapy, and few (22%) were skeptical about the usefulness of pharmacogenomics. Despite this enthusiasm, 87% said their awareness about pharmacogenomic information is lacking. Feeling well-informed about pharmacogenomics was directly related to years in practice/experience: only 38% of trainees reported being well-informed, compared to 46% of those with 1-10 years of experience, and nearly two-thirds with 11+ years (P < 0.05). Regarding barriers, providers reported uncertainty about availability of testing, turnaround time and whether testing is worth financial costs.</p><p><strong>Conclusions: </strong>Anesthesiology, critical care and pain medicine providers are optimistic about the potential clinical utility of pharmacogenomics, but are uncertain about practical aspects of testing and desire clear guidelines on the use of results. These findings may inform future institutional efforts toward greater integration of genomic results to improve medication-related outcomes.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"32 3","pages":"79-86"},"PeriodicalIF":2.6,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8940738/pdf/nihms-1728765.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10233636","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":"Incorporating G6PD genotyping to identify patients with G6PD deficiency.","authors":"Sarah A Morris,&nbsp;Kristine R Crews,&nbsp;Randall T Hayden,&nbsp;Clifford M Takemoto,&nbsp;Wenjian Yang,&nbsp;Donald K Baker,&nbsp;Ulrich Broeckel,&nbsp;Mary V Relling,&nbsp;Cyrine E Haidar","doi":"10.1097/FPC.0000000000000456","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000456","url":null,"abstract":"<p><p>Glucose-6-phosphate-dehydrogenase (G6PD) deficiency is a common X-linked enzyme disorder associated with hemolytic anemia after exposure to fava beans or certain medications. Activity testing is the gold standard for detecting G6PD deficiency; however, this test is affected by various hematologic parameters. Clinical G6PD genotyping is now included in pharmacogenetic arrays and clinical sequencing efforts and may be reconciled with activity results. Patients (n = 1391) enrolled on an institutional pharmacogenetic testing protocol underwent clinical G6PD genotyping for 164 G6PD variants. An algorithm accounting for known interferences with the activity assay is proposed. We developed clinical decision support alerts to inform prescribers when high-risk medications were prescribed, warning of gene-drug interactions and recommending therapy alteration. Of 1391 patients with genotype results, 1334 (95.9%) patients were predicted to have normal G6PD activity, 30 (2.1%) were predicted to have variable G6PD activity and 27 (2%) were predicted to have deficient G6PD activity. Of the 417 patients with a normal genotype and an activity result, 415 (99.5%) had a concordant normal G6PD phenotype. Of the 21 patients with a deficient genotype and an activity result, 18 (85.7%) had a concordant deficient activity result. Genotyping reassigned phenotype in five patients with discordant genotype and activity results: three switched from normal to deficient, and two switched from deficient to normal. G6PD activity and genotyping are two independent testing methods that can be used in conjunction to assign a more informed G6PD phenotype than either method alone.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"32 3","pages":"87-93"},"PeriodicalIF":2.6,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8976699/pdf/nihms-1730117.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10582470","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":"PharmGKB summary: heparin-induced thrombocytopenia pathway, adverse drug reaction.","authors":"Elise Miller, Charles Norwood, Jason B Giles, Rachel Huddart, Jason H Karnes, Michelle Whirl-Carrillo, Teri E Klein","doi":"10.1097/FPC.0000000000000465","DOIUrl":"10.1097/FPC.0000000000000465","url":null,"abstract":"","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"32 3","pages":"117-124"},"PeriodicalIF":1.7,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8988468/pdf/nihms-1771746.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10232192","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":"In-vitro characterization of coding variants with predicted functional implications in the efflux transporter multidrug resistance protein 4 (MRP4, ABCC4).","authors":"Jaymie Mailloux,&nbsp;Samantha Medwid,&nbsp;Amanda Facey,&nbsp;Inmo Sung,&nbsp;Laura E Russell,&nbsp;Rommel G Tirona,&nbsp;Richard B Kim,&nbsp;Ute I Schwarz","doi":"10.1097/FPC.0000000000000459","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000459","url":null,"abstract":"<p><p>MRP4 (gene ABCC4) is a polymorphic efflux transporter that has been implicated in drug-induced toxicity. We selected ten commonly observed MRP4 coding variants among Europeans for experimental characterization including nine variants predicted to be deleterious or functional (combined annotation-dependent depletion score >15). We assessed protein localization and activity by quantifying intracellular accumulation of two prototypic substrates, taurocholic acid (TCA) and estradiol 17-β-glucuronide (E217βG), in HEK293T over-expressing MRP4 wildtype or variant where cellular substrate loading was optimized through co-transfection with an uptake transporter. V458M, a novel variant not previously studied, and T1142M, showed reduced activity compared to MRP4 wildtype for E217βG and TCA (P < 0.01), while L18I, G187W, K293E, and R531Q moderately increased activity in a substrate-dependent manner. Protein expression analysis indicated reduced cell surface expression for V458M (P < 0.01) but not T1142M compared to wildtype. Reduced activity may result from altered surface expression (V458M) or intrinsic activity as both variants map within the nucleotide-binding domains of MRP4. G187W showed a trend for reduced surface expression (P = 0.054) despite transport comparable or increased to wildtype suggesting enhanced intrinsic activity. Our findings suggest moderately altered MRP4 activity in six out of nine predicted functional variants with likely different mechanisms and substrate-specific effects. Cell-based studies using multiple known substrates are warranted to more accurately predict functional variants in this clinically important transporter.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"32 3","pages":"111-116"},"PeriodicalIF":2.6,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10288369","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":"Contribution of APOA5, APOC3, CETP, ABCA1 and SIK3 genetic variants to hypertriglyceridemia development in Mexican HIV-patients receiving antiretroviral therapy.","authors":"Jonathan Saúl Bautista-Martínez,&nbsp;José Antonio Mata-Marín,&nbsp;Jorge Luis Sandoval-Ramírez,&nbsp;Alberto Chaparro-Sánchez,&nbsp;Bulmaro Manjarrez-Téllez,&nbsp;Luis Antonio Uribe-Noguez,&nbsp;Jesús Gaytán-Martínez,&nbsp;Mireya Núñez-Armendáriz,&nbsp;Arcenio Cruz-Sánchez,&nbsp;Nohemí Núñez-Rodríguez,&nbsp;Martínez-Abarca Iván,&nbsp;Georgina Selene Morales-González,&nbsp;Juan Pablo Álvarez-Mendoza,&nbsp;Edgar Pérez-Barragán,&nbsp;Jussara Ríos-De Los Ríos,&nbsp;Gerson Gabriel Contreras-Chávez,&nbsp;Denisse Marielle Tapia-Magallanes,&nbsp;Rosa Maria Ribas-Aparicio,&nbsp;Mónica Díaz-López,&nbsp;Azucena Olivares-Labastida,&nbsp;Alejandro Gómez-Delgado,&nbsp;Javier Torres,&nbsp;Antonio Miranda-Duarte,&nbsp;Juan C Zenteno,&nbsp;Ericka Nelly Pompa-Mera","doi":"10.1097/FPC.0000000000000458","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000458","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the impact of single nucleotide polymorphisms (SNPs) from APOA5, APOC3, CETP, ATP binding cassette transporter A1 and SIK3 genes in the development of hypertriglyceridemia in HIV patients under antiretroviral therapy.</p><p><strong>Material and methods: </strong>A case-control study was developed. Leukocytic genomic DNA was extracted and genotyping for SNPs rs662799, rs964184, rs5128, rs2854116, rs2854117, rs3764261, rs4149310, rs4149267 and rs139961185 was performed by real time-PCR using TaqMan allelic discrimination assays, in Mexican mestizo patients with HIV infection, with hypertriglyceridemia (>1.7 mmol/L) under antiretroviral therapy. Genetic variants were also investigated in a control group of normolipidemic HIV patients (≤ 1.7 mmol/L). Haplotypes and gene interactions were analyzed.</p><p><strong>Results: </strong>A total of 602 HIV patients were genotyped (316 cases and 286 controls). Age and antiretroviral regimen based on protease inhibitors were associated with hypertriglyceridemia (P = 0.0001 and P = 0.0002. respectively). SNP rs964184 GG genotype in APOA5 gene exhibited the highest association with hypertriglyceridemia risk (OR, 3.2, 95% CI, 1.7-5.8, P = 0.0001); followed by SNP rs139961185 in SIK3 gene (OR = 2.3; (95% CI, 1.1-4.8; P = 0.03 for AA vs. AG genotype; and APOC3 rs5128 GG genotype, (OR, 2.2; 95% CI, 1.1-4.9; P = 0.04) under codominant models. These associations were maintained in the adjusted analysis by age and protease inhibitors based antiretroviral regimens.</p><p><strong>Conclusions: </strong>This study reveals an association between rs964184 in APOA5; rs5128 in APOC3 and rs139961185 in SIK3 and high triglyceride concentrations in Mexican HIV-patients receiving protease inhibitors. These genetic factors may influence the adverse effects related to antiretroviral therapy.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"32 3","pages":"101-110"},"PeriodicalIF":2.6,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10582472","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":"Psychotropic prescribing rates and pharmacogenomic testing implications for autism in the Canadian primary care sentinel surveillance network.","authors":"Zeeshan Ahmed,&nbsp;Sylvia Hao,&nbsp;Tyler Williamson,&nbsp;Carly A McMorris,&nbsp;Chad A Bousman","doi":"10.1097/FPC.0000000000000457","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000457","url":null,"abstract":"<p><strong>Objective: </strong>To estimate prescribing rates of psychotropic drugs to individuals with autism and the proportion of these individuals who could benefit from pharmacogenetic testing.</p><p><strong>Methods: </strong>Prescribing data for 92 psychotropic drugs, including 31 antidepressants, 22 antipsychotics, 14 mood stabilizer/antiepileptics, 17 anxiolytic/hypnotics and eight antiadrenergic/psychostimulant were retrieved from medical records of 787 (613 males) autistic individuals who sought treatment from a primary care office enrolled in the Canadian Primary Care Sentinel Surveillance Network between 2012 and 2014. Each prescribed drug was cross-referenced with pharmacogenomic-based prescribing guidelines published by the Clinical Pharmacogenetics Implementation Consortium, the Dutch Pharmacogenetics Working Group, and the Canadian Pharmacogenomics Network for Drug Safety.</p><p><strong>Results: </strong>More than half (58%) of the participants were prescribed a psychotropic drug and 37% were prescribed two or more psychotropic drugs concurrently. Among the 83 psychotropic drugs examined, 54 (65%) were prescribed to one or more participants during the study's observation period. The ten most frequently prescribed psychotropics were methylphenidate (16.3%), risperidone (12.8%), lorazepam (12.1%), fluoxetine (7.9%), sertraline (7.1%), quetiapine (6.9%), aripiprazole (6.1%), lisdexamfetamine (5.8%), citalopram (5.6%) and clonazepam (4.8%). Seventeen (32%) of the 54 psychotropic drugs prescribed were linked to a pharmacogenomic-based prescribing guideline, including risperidone, sertraline, aripiprazole and citalopram.</p><p><strong>Conclusions: </strong>Our findings suggest primary care providers in Canada prescribe a wide range of psychotropics to their patients with autism, some of which may benefit from the integration of pharmacogenomic information into their treatment planning.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"32 3","pages":"94-100"},"PeriodicalIF":2.6,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10233631","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":"Background sensitivity to chemotherapy-induced nausea and vomiting and response to antiemetics in paediatric patients: a genetic association study.","authors":"Astrid Eliasen,&nbsp;Jonatan Kornholt,&nbsp;René Mathiasen,&nbsp;Karin Wadt,&nbsp;Ulrik Stoltze,&nbsp;Jesper Brok,&nbsp;Catherine Rechnitzer,&nbsp;Kjeld Schmiegelow,&nbsp;Kim Dalhoff","doi":"10.1097/FPC.0000000000000460","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000460","url":null,"abstract":"<p><p>Chemotherapy-induced nausea and vomiting (CINV) remains a common adverse effect for children with cancer. In children, chemotherapy emetogenicity and patient factors such as susceptibility to motion sickness and age group determine a patient's risk of CINV. Besides known risk factors, genetic factors may play a role in interindividual variation in the occurrence of CINV. We investigated the influence of candidate gene polymorphisms on the efficacy of antiemetics and on the background sensitivity to CINV in children. This prospective study included 100 children with cancer (median age 6.4 years, range 0.8-17.9) who received moderately to highly emetogenic chemotherapy. Participants registered nausea and vomiting episodes in a mobile app. Genotypes were determined by whole-genome sequencing (n = 79) or Sanger sequencing (n = 21) for 71 genetic polymorphisms involved in motion sickness and antiemetic pathways. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate associations between acute CINV and genotypes adjusting for susceptibility to motion sickness and age group. Rs3782025 in the 5-hydroxytryptamine type 3 (5-HT3) receptor gene (HTR3B) [minor allele frequency (MAF): 0.48] affected response to 5-HT3 receptor antagonists; acute CINV occurred in 76% of patients with GA/AA genotypes and in 41% of patients with GG genotype (OR 5.59; 95% CI 1.74-17.9, dominant genetic model). Rs2975226 in the dopamine transporter gene (SLC6A3) (MAF: 0.54) was associated with acute CINV (OR 5.79; 95% CI 1.09-30.67, recessive genetic model). Polymorphisms in HTR3B and SLC6A3 may contribute to the variability in response to antiemetic prophylaxis for CINV in children.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"32 2","pages":"72-78"},"PeriodicalIF":2.6,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10235621","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":"Comprehensive characterization of pharmacogenetic variants in TPMT and NUDT15 in children with acute lymphoblastic leukemia.","authors":"Takaya Moriyama,&nbsp;Wenjian Yang,&nbsp;Colton Smith,&nbsp;Ching-Hon Pui,&nbsp;William E Evans,&nbsp;Mary V Relling,&nbsp;Smita Bhatia,&nbsp;Jun J Yang","doi":"10.1097/FPC.0000000000000453","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000453","url":null,"abstract":"<p><p>Thiopurines [e.g. 6-mercaptopurine (6MP)] are essential for the cure of acute lymphoblastic leukemia (ALL) but can cause dose-limiting hematopoietic toxicity. Germline variants in drug-metabolizing enzyme genes TPMT and NUDT15 have been linked to the risk of thiopurine toxicity. However, the full spectrum of genetic polymorphism in these genes and their impact on the pharmacological effects of thiopurines remain unclear. Herein, we comprehensively sequenced the TPMT and NUDT15 genes in 685 children with ALL from the Children's Oncology Group AALL03N1 trial and evaluated their association with 6MP dose intensity. We identified 6 and 5 coding variants in TPMT and NUDT15 respectively, confirming the association at known pharmacogenetic variants. Importantly, we discovered a novel gain-of-function noncoding variants in TPMT associated with increased 6MP tolerance (rs12199316), with independent validation in 380 patients from the St. Jude Total Therapy XV protocol. Located adjacent to a regulatory DNA element, this intergenic variant was strongly associated TPMT transcription, with the variant allele linked to higher expression (P = 2.6 × 10-9). For NUDT15, one noncoding common variant, rs73189762, was identified as potentially related to 6MP intolerance. Collectively, we described pharmacogenetic variants in TPMT and NUDT15 associated with thiopurine sensitivity, providing further insights for implementing pharmacogenetics-based thiopurine individualization.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"32 2","pages":"60-66"},"PeriodicalIF":2.6,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8702453/pdf/nihms-1726174.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10288365","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":"Comparison of clinical pharmacogenetic recommendations across therapeutic areas.","authors":"Tyler Shugg,&nbsp;Amy L Pasternak,&nbsp;Jasmine A Luzum","doi":"10.1097/FPC.0000000000000452","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000452","url":null,"abstract":"<p><strong>Objectives: </strong>Evaluations from pharmacogenetics implementation programs at major US medical centers have reported variability in the clinical adoption of pharmacogenetics across therapeutic areas. A potential cause for this variability may involve therapeutic area-specific differences in published pharmacogenetics recommendations to clinicians. To date, however, the potential for differences in clinical pharmacogenetics recommendations by therapeutic areas from prominent US guidance sources has not been assessed. Accordingly, our objective was to comprehensively compare essential elements from clinical pharmacogenetics recommendations contained within Clinical Pharmacogenetics Implementation Consortium guidelines, US Food and Drug Administration drug labels and clinical practice guidelines from US professional medical organizations across therapeutic areas.</p><p><strong>Methods: </strong>We analyzed clinical pharmacogenetics recommendation elements within Clinical Pharmacogenetics Implementation Consortium guidelines, US Food and Drug Administration drug labels and professional clinical practice guidelines through 05/24/19.</p><p><strong>Results: </strong>We identified 606 unique clinical pharmacogenetics recommendations, with the most recommendations involving oncology (217 recommendations), hematology (79), psychiatry (65), cardiovascular (43) and anesthetic (37) medications. Within our analyses, we observed considerable variability across therapeutic areas within the following essential pharmacogenetics recommendation elements: the recommended clinical management strategy; the relevant genetic biomarkers; the organizations providing pharmacogenetics recommendations; whether routine genetic screening was recommended; and the time since recommendations were published.</p><p><strong>Conclusions: </strong>On the basis of our results, we infer that observed differences in clinical pharmacogenetics recommendations across therapeutic areas may result from specific factors associated with individual disease states, the associated genetic biomarkers, and the characteristics of the organizations providing recommendations.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"32 2","pages":"51-59"},"PeriodicalIF":2.6,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8702450/pdf/nihms-1726173.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10288366","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}