Pharmacogenomics最新文献

Purpose: This work was designed to identify the pharmacogenetic profile of Brazilian psychiatric patients receiving psychoactive drug treatment according to ethnicity. Methods: Based on the GnTech^® database, this cross-sectional study analyzed data from self-reported sociodemographic and genetic results from the next-generation sequencing panel composed of 26 pharmacogenes from 359 psychotropic drug users. Results: Variant frequencies of multiple pharmacogenes presented differences between ethnicities (CYP3A5, CYP2D6, CYP1A2, CYP2B6, CYP3A4, UGT1A4, UGT2B15, ABCB1 rs1045642, ADRA2A rs1800544, COMT rs4680, GRIK4 rs1954787, GSK3B rs334558, GSK3B rs6438552, HTR1A rs6295, HTR2A rs7997012, HTR2C rs1414334, MTHFR rs1801131, OPRM1 rs1799971 and 5-HTTLPR), endorsing the necessity of individual-level analyses in drug treatment. Conclusion: A discussion of pharmacogenomic test implementation in psychiatric clinical practice is needed to improve treatment choices, especially in Brazil, a multiethnic country.

Background: Abacavir (ABC) in combination with other antiretroviral drugs, is used to treat people living with HIV (PLWH). However, it is linked to a fatal hypersensitivity reaction in susceptible individuals, and is strongly associated with the HLA-B*57:01 allele. Materials & methods: A total of 152 patients, 50 PLWH and 102 HIV-1 negative patients, were assessed for the HLA-B*57:01 allele through a sequence-specific primer PCR. Results: All PLWH tested negative for the HLA-B*57:01 allele, but two HIV-negative patients were found to have HLA-B*57, with one of them expressing the HLA-B*57:01 allele. Conclusion: Given the low prevalence of this risk allele in the population, testing for the presence of HLA-B*57:01 in PLWH may not provide significant benefit for the reported population.

A woman with ocular hypertension suffered from severe bradycardia, hypotension and syncope attacks in temporal relation with ophthalmic timolol application. Topically applied timolol is nasally absorbed and has been shown to reach potentially relevant systemic concentrations. Timolol is mainly metabolized by CYP2D6, which exhibits interindividual metabolic capacity due to genetic variations. A reactive pharmacogenetic panel test identified the patient as a CYP2D6 homozygous *4 allele carrier, which has been associated with a poor metabolizer phenotype and lacking enzyme activity. Thus, the adverse drug reactions possibly resulted from increased systemic timolol exposure. This case report highlights that pharmacogenetic panel testing can contribute to safe and effective pharmacotherapy, even for topically applied drugs.

The early detection of acute rejection in the allograft is important as it provides an opportunity for timely therapeutic intervention in order to preserve graft function and achieve longer graft survival. Donor-derived cell-free DNA (dd-cfDNA) has emerged as a new biomarker in the field of kidney transplantation. In this review, we used data from various studies to examine the role of dd-cfDNA in comparison to creatinine and donor-specific antibodies in the early detection of transplant rejection. We also reviewed the use of dd-cfDNA in other organ transplants as well as the challenges and potential future direction for dd-cfDNA as a diagnostic tool.

Approximately 70% of individuals diagnosed with autism spectrum disorder (ASD) receive at least one psychotropic medication to treat comorbidities. However, the response to treatment with these drugs is far from satisfactory, with 30-50% of treated patients not responding adequately or developing severe and long-lasting side effects. There is strong evidence of the clinical utility of pharmacogenetics for the personalization of antipsychotic and antidepressant treatments in adult populations. However, the use of pharmacogenetic interventions for the personalization of treatment in ASD populations is minimal. The aim of this review is to summarize the findings of pharmacogenetic studies conducted in subjects with ASD and illustrate their utility in the personalization of treatment with psychoactive drugs in this population group.

Precision medicine has revolutionized clinical care for patients with cancer through the development of targeted therapy, identification of inherited cancer predisposition syndromes and the use of pharmacogenetics to optimize pharmacotherapy for anticancer drugs and supportive care medications. While germline (patient) and somatic (tumor) genomic testing have evolved separately, recent interest in paired germline/somatic testing has led to an increase in integrated genomic testing workflows. However, paired germline/somatic testing has generally lacked the incorporation of germline pharmacogenomics. Integrating pharmacogenomics into paired germline/somatic genomic testing would be an efficient method for increasing access to pharmacogenomic testing. In this perspective, the authors argue for the benefits of implementing a comprehensive approach integrating somatic and germline testing that is inclusive of pharmacogenomics in clinical practice.

Objective & methods: This study tested associations of genotype-predicted activity of CYP3A4, other pharmacogenes, SLC28A7 (rs11648166) and ALPPL2 (rs28845026) with systemic concentrations of the endocrine therapies anastrozole and fulvestrant in SWOG S0226 trial participants. Results: Participants in the anastrozole-only arm with low CYP3A4 activity (i.e. CYP3A4*22 carriers) had higher systemic anastrozole concentrations than patients with high CYP3A4 activity (β-coefficient = 10.03; 95% CI: 1.42, 18.6; p = 0.025). In an exploratory analysis, participants with low CYP2C9 activity had lower anastrozole concentrations and higher fulvestrant concentrations than participants with high CYP2C9 activity. Conclusion: Inherited genetic variation in CYP3A4 and CYP2C9 may affect concentrations of endocrine therapy and may be useful to personalize dosing and improve treatment outcomes.

Background: This study investigated the use of COMT G1947A and OPRM1 A118G polymorphisms as predictive markers for sufentanil epidural analgesia. Methods: The visual analogue scale (VAS) score, and sufentanil consumption of 136 pairs of parturients using sufentanil with lidocaine and ropivacaine for epidural analgesia were used for analysis. Results: OPRM1 AG/GG had lower VAS score difference between fifth and 0 min (1.55 vs 1.87; p = 0.012) and higher consumption (19.65 μg vs 17.11 μg; p = 0.049) than AA carriers. COMT GA/AA had higher VAS score difference than GG carriers (1.86 vs 1.55; p = 0.021). Conclusion: Sufentanil may provide better epidural labor analgesia in OPRM1 AA and COMT GA/AA carriers compared with OPRM1 AG/GG and COMT GG carriers. Clinical Trial Registration: ChiCTR1900026897 (Chinese Clinical Trial Center Registry).