Pharmacogenomics最新文献

Aim: To understand how attitudes toward pharmacogenomic (PGx) testing among healthcare providers varies by specialty. Methods: Providers reported comfort ordering PGx testing and its perceived utility on web-based surveys before and after genetics education. Primary quantitative analyses compared primary care providers (PCPs) to specialty providers at both timepoints. Results: PCPs were more likely than specialty care providers to rate PGx testing as useful at both timepoints. Education increased comfort ordering PGx tests, with larger improvements among PCPs than specialty providers. Over 90% of cardiology and internal medicine providers rated PGx testing as useful at pre- and post-education. Conclusion: PCPs overwhelmingly perceive PGx to be useful, and provider education is particularly effective for improving PCPs' confidence. Education for all specialties will be essential to ensure appropriate integration into routine practice.

Aim: Examining the association between HLA-A/B alleles and different carbamazepine (CBZ)-induced cutaneous adverse reactions in the Chinese population. Methods: A systematic review and meta-analysis of case-control studies was conducted. A systematic search was conducted of PubMed, Embase, the Cochrane Library, National Knowledge Infrastructure, the Chinese Biomedical Literature database and Wanfang Digital Periodicals. Results: 23 studies with a total of 1174 patients were included. In the Han population, HLA-B*15:02 is significantly associated with the increased risk of CBZ-related Stevens-Johnson syndrome/toxic epidermal necrolysis, and this correlation was not related to geographic distribution. HLA-A*31:01, B*38:02 are associated with CBZ-related maculopapular eruption in South Han population. HLA-A*31:01 is associated with CBZ-DRESS in Taiwan Han population. Conclusion: HLA-B*15:02, A*31:01 and B*38:02 genes were found to be involved in the occurrence of CBZ cutaneous adverse reactions in Han Chinese.

Background: Bladder cancer is a common urogenital malignancy characterized by frequent genetic alterations. Histone demethylase gene KDM6A is commonly mutated in bladder cancer. Aim: To review the characteristics of KDM6A and its mutation consequences, and to introduce a potential KDM6A-targeted treatment. Methods: We conducted a comprehensive literature search using two electronic databases, MEDLINE and Cochrane Library, to retrieve topic-related articles from July 2013 to July 2022 using keywords 'KDM6A', 'bladder cancer', 'UTX', 'treatment' and 'mutation'. Five reviewers independently screened literature search results and abstracted data from included studies. Descriptive analysis was conducted and 30 articles were retained. Main Results: A total of 30 articles were retrieved. Experimental and clinical data were collected and grouped by theme. Therapeutic strategies are depicted and organized by tables for a better understanding. Conclusion: This review demonstrates that KDM6A has crucial implications in bladder cancer pathogenesis and treatment.

Aim: To evaluate the prevalence of medications with actionable pharmacogenomic (PGx) safety and efficacy recommendations in patients receiving care from the Veterans Health Administration. Materials & methods: Outpatient prescription data from 2011 to 2021 and any documented adverse drug reactions (ADRs) were reviewed for those who received PGx testing at one Veterans Administration location between November 2019 and October 2021. Results: Among the reviewed prescriptions, 381 (32.8%) were associated with an actionable recommendation based on the Clinical Pharmacogenetics Implementation Consortium (CPIC) prescribing guidelines, with 205 (17.7%) for efficacy concerns and 176 (15.2%) for safety concerns. Among those with a documented ADR for a PGx-impacted medication, 39.1% had PGx results that aligned with CPIC recommendations. Conclusion: Medications with actionable PGx recommendations for safety and efficacy concerns are received with similar frequency, and most patients who have undergone PGx testing at the Phoenix Veterans Administration have received medications that may be impacted by PGx testing.

Tweetable abstract Pretreatment UGT1A1 genotyping and a 70% irinotecan dose intensity in poor metabolizers is safe, feasible, cost-effective and essential for safe irinotecan treatment in cancer patients. It is time to update guidelines to swiftly enable the implementation of UGT1A1 genotype-guided irinotecan dosing in routine oncology care.

Meaningful clinical decision support (CDS) recommendations are vital for implementation of pharmacogenomics (PGx) into routine clinical care. PGx CDS alerts include interruptive and noninterruptive alerts. The objective of this study was to evaluate provider ordering behavior after noninterruptive alerts are displayed. A retrospective manual chart review was conducted from the time of noninterruptive alert implementation to the time of data analysis to determine congruence with CDS recommendations. The congruence rate for noninterruptive alerts was 89.8% across all drug-gene interactions. The drug-gene interaction with the most alerts for analysis included metoclopramide (n = 138). The high rate of medication order congruence after noninterruptive alerts were deployed suggests this modality may be appropriate for PGx CDS as a method for best practice adherence.

Objective: This meta-analysis was designed to investigate the associations between SLCO1B1, APOE and CYP2C9 and the lipid-lowering effects and pharmacokinetics of fluvastatin. Methods: Studies were searched from inception to March 2023, including three SNPs related to fluvastatin, SLCO1B1, CYP2C9 and APOE. Weighted mean differences and corresponding 95% CIs were analyzed to evaluate the associations between SNPs and outcomes. Results: SLCO1B1 521T>C was associated with lower total cholesterol and low-density lipoprotein reduction. Patients carrying 521CC or total cholesterol had a significantly higher area under the curve than those carrying 521TT, but no significant difference existed. Conclusion: CYP2C9 and SLCO1B1 may be associated with the efficacy and pharmacokinetics of fluvastatin.

Background: 6-mercaptopurine usage is associated with myelotoxicity and increased risk in patients carrying metabolism-related genetic variations. This study aimed to determine the frequency of candidate gene polymorphisms and their association with 6-mercaptopurine intolerance. Methods: A total of 41 patients on acute lymphoblastic leukaemia treatment were genotyped for TPMT and NUDT15 (rs116855232) alleles, and their association with dose intensity was analyzed. Results: The defective TPMT*3C allele frequency was 9.8%. The median maintenance dose intensity for TPMT*1/*3C participants was considerably lower (47%) when compared with the TPMT*1/*1 wild-type (77%), although not statistically significant. Conclusion: This is the first pharmacogenetics study carried out in a black Zimbabwean leukemia patient cohort. The high defective TPMT*3C (9.8%) allele frequency points to the potential utility of pharmacogenetics testing for safe usage of 6-mercaptopurine in this population.

Aim: Few genome-wide association studies (GWASs) have been conducted to identify predictors of drug concentrations. The authors therefore sought to discover the pharmacogenomic markers involved in metoprolol pharmacokinetics. Patients & methods: The authors performed a GWAS of a cross-sectional study of 993 patients from the Montreal Heart Institute Biobank taking metoprolol. Results: A total of 391 and 444 SNPs reached the significance threshold of 5 × 10^-8 for metoprolol and α-OH-metoprolol concentrations, respectively. All were located on chromosome 22 at or near the CYP2D6 gene, encoding CYP450 2D6, metoprolol's main metabolizing enzyme. Conclusion: The results reinforce previous findings of the importance of the CYP2D6 locus for metoprolol concentrations and confirm that large biobanks can be used to identify genetic determinants of drug pharmacokinetics at a GWAS significance level.

Aim: To assess knowledge, confidence and perceptions of healthcare professionals specializing in primary care and pain management at Brigham and Women's Hospital, related to clinical pharmacogenomics (PGx). Methods: A 25-question online survey was distributed to 328 Brigham and Women's Hospital clinicians for analysis. Results: Thirty-four clinicians completed the survey. Respondents had minimal experience with PGx and limited awareness of PGx resources. Although respondents expressed belief that PGx has utility to improve medication-related patient outcomes, many lack confidence to apply PGx results to their practice. For clinical drug-gene questions relevant to primary care and/or pain management, respondents scored poorly. Conclusion: More clinician education is needed for appropriate utilization of PGx in clinical practice as it pertains to primary care and pain management.