Pharmacogenomics最新文献

Pharmacogenomics (PGx) is a practice that investigates the link between genetic differences and drug response in patients. This can improve treatment effectiveness and reduce harmful side effects. However, has yet to be adequately realized in developing nations. Three surveys were conducted between November 2022 to March 2023 in Egypt and Lebanon. The first survey assessed availability of PGx testing in different healthcare facilities; the second one assessed knowledge, interest and attitude toward learning about PGx among pharmacists and physicians; and the third one assessed interest in providing PGx education at academic levels. In Egypt, a few of the surveyed healthcare facilities are conducting some form of pharmacogenetic testing. In Lebanon, very few germline pharmacogenomic tests are offered in Greater Beirut's leading hospitals, and no other testing was recorded. PGx education attracts considerable interest, with 34.3% of pharmacists very interested and 48.8% interested. Similarly, 24.8% of total physicians were very interested while 44.8% were interested. Academic professionals in the surveyed institutions in both countries agreed on the need for educational programs in PGx and 78.2% agreed that there were good opportunities for implementing PGx testing. These findings clearly indicate the need to develop and implement educational programs in PGx in the Middle-East.

Aim: To evaluate the feasibility and impact of using CYP2C19 genotype to guide selection of antiplatelet therapy in patients undergoing intracranial aneurysm treatment with a flow diversion stent in a real-world clinical setting.Patients & methods: A single-center, retrospective, observational cohort study was conducted in 112 patients undergoing intracranial aneurysm repair with flow-diversion stenting from 2014 to 2021. Data were abstracted from health records. The frequency of clopidogrel or alternative therapy (ticagrelor or prasugrel) use was compared across CYP2C19 status (intermediate or poor metabolizer [IM/PM] vs. normal, rapid, or ultrarapid metabolizer [NM/RM/UM]).Results: In the study population, CYP2C19 genotype testing was performed on 110 (98.2%) patients; of these, 106 (97.2%) had results available prior to the stent procedure and 28 (25.5%) were IM/PMs. Alternative therapy was used more frequently in IM/PMs compared with NM/RM/UMs (57.1 vs. 8.5%, respectively, p < 0.0001). The frequency of thromboembolic events over 12 months did not significantly differ across clopidogrel-treated IM/PMs, clopidogrel-treated NM/RM/UMs and patients on alternative therapy (p = 0.352); although, event numbers were low.Conclusion: A pre-emptive CYP2C19 genotyping strategy to guide antiplatelet therapy selection in intracranial aneurysm repair patients is feasible in a real-world clinical setting. Larger studies are needed to assess the impact on clinical outcomes.

Aim: Implementation of CYP2C19 point-of-care (POC) pharmacogenetic (PGx) testing with personalized treatment recommendations. Methods: POC CYP2C19 genotyping plus expert evaluation of risk factors for ischemic and bleeding events. Results: 167 patients underwent PGx testing, 54 (32.3%) were CYP2C19 loss of function carriers, and POC versus standard PGx analysis results for *2 and *3 variants matched in 100%. Antiplatelet therapy was adjusted in 44 patients (26.3%), but always required consideration of patient-specific factors. Conclusion: CYP2C19 POC-PGx is reliable and offers clinically relevant advantages for immediate evidence-based adaptations of antiplatelet therapy, whereas in less acute cases conventional PGx testing can also have advantages. Antiplatelet therapy has become more complex, and implementation of PGx-based personalized antiplatelet therapy requires complementary expert knowledge.

Purpose: To compare minor allele frequencies (MAFs) of psychiatric drug response variants in a Brazilian admixed cohort with global populations and other Brazilian groups. Methods: PharmGKB MAFs were gathered from publicly available genetic datasets for Brazil and worldwide. Results: Among 146 variants in CYP2D6 and CYP2C19, 41 were present in Brazil, mostly rare (MAF <1%). 11 variants showed significant MAF differences with large effect sizes compared with global populations. CYP2C19*3 (rs4986893), CYP2C19*17 (rs12248560), CYP2D6*17 (rs28371706-A) and CYP2D6*29 (rs61736512) exhibited higher frequencies in Brazil, with the latter three also differing from other Brazilian groups. Conclusion: This study highlights significant pharmacogenomic diversity in Brazil and globally, underscoring the need for more research in personalized psychiatric drug therapy.

Background: Previous differences in guideline recommendation strength for CYP2C19 intermediate metabolizers may have limited genotype (PGx)-optimal post-percutaneous coronary intervention antiplatelet prescribing.Results: In this single-center retrospective observational cohort study of CYP2C19 intermediate metabolizers, patients prescribed PGx-optimal therapy were younger and less likely on anticoagulation (2 vs 12%; p = 0.006). More patients prescribed PGx-optimal therapy possessed commercial insurance (36 vs 7%; p < 0.001), which was a predictor for PGx-optimal selection (OR: 6.464; 95% CI: 2.386-17.516; p < 0.001).Conclusion: Anticoagulation use was significantly associated with clopidogrel use (OR: 0.138; 95% CI: 0.026-0.730; p = 0.020). No statistical difference in composite major adverse cardiovascular events (5 vs 14%; p = 0.173) or bleeding (8 vs 6%; Not significant) was observed between PGx-optimal and PGx-suboptimal therapy.

Aim: To explore general practitioners' (GPs) views on implementing pharmacogenomic testing in Australian general practice.Methods: Semi-structured interviews were conducted with nine GPs in Australia, recruited from primary care networks. Interviews were analyzed using thematic analysis. Themes were mapped onto the Consolidated Framework for Implementation Research domains.Results: Barriers to implementation included lack of knowledge, education, standardized pharmacogenomic reports and national clinical guidelines and financial inaccessibility. Facilitators included positive exposure to pharmacogenomics, peer influences, interdisciplinary collaboration and proven clinical utility. Current uptake was minimal; however, GPs shared positive perceptions of clinical use.Conclusion: Recommendations for successful implementation include building and disseminating clinical evidence, developing national guidelines and standardized reports, incorporation into formal education and increasing financial accessibility.

Aim: Associations between gene variants and opioid net effect are unclear. We conducted an exploratory pharmacogenetic analysis of 35 gene variants and opioid response in advanced cancer. Patients & methods: This multi-center prospective cohort study included clinical data, questionnaires (pain and adverse effects) and DNA (blood). Negative binomial regression and logistic regression were used. Results: Within 54 participants, eight statistically significant associations (p = 0.002-0.038) were observed between gene variants and opioid dose, pain scores or adverse effects, the majority being within the neuroimmune TLR4 pathway (IL1B [rs1143634], IL2 [rs2069762], IL6 [rs1800795], BDNF [rs6265]) and ARRB2 pathway (ARRB2 [rs3786047], DRD2 [rs6275]). Conclusion: Neuroimmune pathway genes may contribute to differences in opioid response in cancer and may be included in future similar studies.

Tweetable abstract Present evidence supports the use of intensified pharmacologic monitoring of #imatinib including #TherapeuticDrugMonitoring and #PGx to improve outcomes in patients with GI stromal tumor. Future studies need to address emerging questions to facilitate implementation in clinics.

Aims: To evaluate the association between SLCO1B1 gene polymorphisms and susceptibility of antituberculosis drug-induced hepatotoxicity (ATDH). Methods: We searched the PubMed, Cochrane Library, Embase, Web of Science, Wan Fang and China National Knowledge Infrastructure database from inception to 2022. Results: Nine case-control studies with 1129 cases and 2203 controls were included. Among four SNPs reported in two or more studies, the final results indicated that SNP rs4149014 was significantly associated with decreased ATDH risk (dominant model, odds ratio: 0.73; 95% CI: 0.55-0.97; p = 0.03; allele model, odds ratio: 0.69; 95% CI: 0.55-0.86; p = 0.001), and the trial sequential analysis also confirmed this significant association. Conclusion: SLCO1B1 gene SNP rs4149014 was significantly associated with lower risk of ATDH susceptibility.

Aim: Pre-emptive testing of pharmacogenomic (PGx) variations has potential to improve medication safety and effectiveness; however, testing is not routine. Given the newfound payor coverage of multigene testing and the potential value of testing within aging patients, it is imperative to test local PGx testing capabilities, report results to patients and providers, and determine the value of testing. Materials & methods: We designed a randomized clinical pilot of a pre-emptive PGx testing process using the electronic health record compared with usual care among an aging primary care population. Results & conclusion: The impact of the program on prescribing patterns, healthcare utilization and costs of care will be evaluated. We hypothesize that implementation of a pre-emptive multigene PGx panel is feasible among elderly, polypharmacy, primary care patients, measured by the number of enrolled patients with PGx results entered in the medical record. Health system wide PGx implementation, including capacity needed to integrate these valuable results, is also described.