Pharmacogenomics最新文献

We developed novel electronic phenotyping algorithms for the BioMe biobank data, which accurately identified angiotensin converting enzyme inhibitor (ACEi)-induced angioedema cases and controls. A survey was mailed to all 1075 patients and 91 were returned. Over a third reported that prescribing physicians had not discussed with them the concepts of interindividual drug response variability or adverse event risk, and 73% of patients were previously unaware of pharmacogenomics; however, most patients were interested in having pharmacogenomic testing. Moreover, 67% of patients indicated that pharmacogenomic testing would positively influence their medication compliance. In addition to identifying an innovative approach to define biobank cohorts for pharmacogenomic studies, these results indicate that patients are interested in pharmacogenomic testing, which could translate to improved adherence.

Aim: To advance clinical adoption and implementation of pharmacogenomics (PGx) testing, barriers and facilitators to these efforts must be understood. This study identified and examined barriers and facilitators to active implementation of a PGx program across multiple clinic settings in an academic healthcare system. Materials & methods: 28 contributors to the PGx implementation (e.g., clinical providers, informatics specialists) completed an interview to elicit their perceptions of the implementation. Results: Qualitative analysis identified several barriers and facilitators that spanned different stages of the implementation process. Specifically, unclear test payment mechanisms, decision support tool development, rigid workflows and provider education were noted as barriers to the PGx implementation. A multidisciplinary implementation team and leadership support emerged as key facilitators. Furthermore, participants also suggested strategies to overcome or maintain these factors. Conclusion: Assessing real-world implementation perceptions and suggested strategies from a range of implementation contributors facilitates a more comprehensive framework and best-practice guidelines for PGx implementation.

Tweetable abstract Accurate variant interpretation has become a key bottleneck for the translation of an individual's pharmacogenome into actionable recommendations. We recommend an integrated use of multiplexed assays, structure-based predictions and biobank data to develop more accurate effect predictors.

Aim: Identify oncology healthcare providers' attitudes toward barriers to and use cases for pharmacogenomic (PGx) testing and implications for prescribing anticancer and supportive care medications. Materials & methods: A questionnaire was designed and disseminated to 71 practicing oncology providers across the MedStar Health System. Results: 25 of 70 (36%) eligible oncology providers were included. 88% were aware of PGx testing and 72% believed PGx can improve care. Of providers who had ordered a medication with PGx implications in the past month, interest in PGx for anticancer (90-100%) and supportive care medications (>75%) was high. Providers with previous PGx education were more likely to have ordered a test (odds ratio: 7.9; 95% CI: 1.1-56; p = 0.0394). Conclusion: Oncology provider prescribing practices and interest in PGx suggest opportunities for implementation.

With the aim of integrating clinical pharmacology with pharmacogenomics and providing a platform to gather clinicians, academicians, diagnostic laboratory personnel and scientists from related domains, the International Conference on Clinical Pharmacology and Pharmacogenomics 2023 (ICCPP 2023) was jointly organized by the Department of Pharmacology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, India and the CANSEARCH research platform in Pediatric Oncology and Hematology, University of Geneva, Geneva, Switzerland. The conference was held on 31 August and 1 September 2023, as a continued Indo-Swiss scientific exchange event series. In this report we describe the proceedings of this conference for the benefit of peers who could not attend the conference but are interested in knowing about the scientific program in detail.

Background: CYP2C19 is important in the metabolism of clopidogrel and several antidepressants. This study aimed to characterize the distribution of CYP2C19 star alleles (haplotypes) across diverse African populations compared with global populations. Methods: CYP2C19 star alleles and diplotypes were called from high coverage genomes using the StellarPGx pipeline. Results: CYP2C19*1 (51%), *2 (17%) and *17 (22%) were the most common star alleles across African populations in this study. It was observed that 3% of African participants had potentially novel CYP2C19 haplotypes. Conclusion: This study supports the necessity for CYP2C19 pharmacogenetic testing in African and global clinical settings, as well as the importance of comprehensive star allele characterization in the African context.

As substrates of CYP2C8, CYP3A4/5 and CYP2D6, chloroquine's (CQ) and hydroxychloroquine's (HCQ) efficacy and safety may be affected by variants in the genes encoding these enzymes. This paper aims to assimilate the current evidence on the pharmacogenomics of CQ/HCQ and to identify risk phenotypes affecting the safety or efficacy of these drugs. It has been found that some CYP3A5, CYP2D6 and CYP2C8 genetic variants may affect the safety or effectiveness of CQ/HCQ. The phenotypes predictively representing ultra-rapid and poor metabolizers have been considered high-risk phenotypes. After considering these high-risk phenotypes in different ethnic groups, it is predicted that a considerable proportion of patients taking CQ/HCQ may be at risk of either therapeutic failure or severe toxicities.

Aim: To describe the diversity of pharmacogenetic variants of statins among Sri Lankans. Materials & methods: Variant data of relevant genes were obtained from an anonymized database of 426 Sri Lankans. Minor allele frequencies (MAFs) were compared with published data from other populations. Results: The MAF of SLCO1B1*5 (rs4149056 [T>C]) was 18.19% (95% CI: 14.53-21.85). MAFs of CYP2C9*2 (rs1799853 [C>T]) and CYP2C9*3 (rs1057910 [A>C]) were 2.58% (95% CI: 1.08-4.08) and 10.30% (95% CI: 7.75-13.61), respectively. MAFs of rs2231142 (G>T) (ABCG2), rs7412 (C>T) (APOE) and rs20455 (A>G) (KIF6) variants were 10.68% (95% CI: 7.76-13.60), 3.52% (95% CI: 1.77-5.27) and 50.7% (95% CI: 45.96-55.45), respectively. Compared with western/other Asian populations, rs20455 (A>G), CYP2C9*3 (A>C) and SLCO1B1*5 (T>C) variants were significantly higher in Sri Lankans. Conclusion: Variants that affect efficacy of statins (KIF6 [rs20455], CYP2C9*3) and increase risk of statin-induced myotoxicity (SLCO1B1*5 and CYP2C9*3) were prevalent in higher frequencies among Sri Lankans compared with western populations.

Aim: Tuberous sclerosis complex (TSC) is a rare disease that produces multisystemic disorders. Everolimus (EVR) is the only immunosuppressive drug approved to control the symptoms and progression of the disease. The aim was to evaluate the genotype-phenotype association to improve the pediatric TSC pharmacotherapeutic outcome. Patients & methods: Ten pediatric TSC patients were recruited. Concomitant treatment and main metabolic enzymes and transporter coding gene variants of EVR were analyzed. Results: Significant associations were found between CYP3A4*22 allele and concomitant treatment with valproic acid (CYP3A4-inhibitor) with a poor metabolizer phenotype and the presence of pneumonia. Conclusion: This is the first pharmacogenetic study of EVR in pediatric TSC patients. The authors propose to consider concomitant treatment and pharmacogenetics due to their multifactorial status.

Intravenous pentamidine is used for prophylaxis against Pneumocystis jirovecii pneumonia, an infection seen in hematopoietic stem cell transplant recipients. Pentamidine is partially metabolized by CYP2C19, which is vulnerable to pharmacogenetic variation. This retrospective study evaluated allogeneic hematopoietic stem cell transplant patients who received intravenous pentamidine as P. jirovecii pneumonia prophylaxis. The primary objective was the association between CYP2C19 phenotype and discontinuation of pentamidine due to drug-related side effects based on univariate logistic regression (N = 81). Ten patients (12.3%) discontinued pentamidine because of side effects. There was no difference in discontinuation between phenotype groups (p = 0.18) or discontinuation due to side effects (p = 0.76). Overall, no association was seen between phenotypes and pentamidine-related side effects (p = 0.475). Drug discontinuation rates and P. jirovecii pneumonia infection rates were low.