Clin Ther. 2023 Jun 8:S0149-2918(23)00135-2. doi: 10.1016/j.clinthera.2023.04.006. Online ahead of print.

ABSTRACT

PURPOSE: The anticoagulation activity of warfarin in populations with CYP2C9, VKORC1, and CYP4F2 variants differs between individuals and is correlated with poor international normalized ratio (INR) control. Pharmacogenetics-guided warfarin dosing has been successfully developed for patients with genetic variations in recent years. However, few real-world data have been used to investigate the INR and warfarin dosage and the time to target INR. This study examined the largest collection of genetic and clinical real-world data related to warfarin to provide further evidence supporting the benefits of pharmacogenetics in clinical outcomes.

METHODS: We retrieved a total of 69,610 INR-warfarin records after the index date from 2,613 patients in the China Medical University Hospital database between January 2003 and December 2019. Each INR reading was obtained from the latest laboratory data after the hospital visit date. Patients with a history of malignant neoplasms or pregnancy before the index date were excluded, as were patients without data on INR measurements after the fifth day of prescription, genetic information, or gender variables. The primary outcomes were the INR and warfarin dosage during days 7, 14, 28, 56, and 84 after prescription. The secondary outcome was the time required to reach the INR ranges of 1.5 to 3.0 and >4.0.

FINDINGS: A total of 59,643 INR-warfarin records from 2188 patients were retrieved. The average INR was higher for homozygous carriers of the minor allele at CYP2C9 and VKORC1 during the first 7 days (1.83 [1.03] [CYP2C9*1] and 2.46 [1.44] [CYP2C9*3], P < 0.001; 1.39 [0.36] [rs9923231 G/G], 1.55 [0.79] [rs9923231 G/A], and 1.96 [1.13] [rs9923231 A/A], P < 0.001) than for the wild-type allele. These patients with variants required lower warfarin doses than those with the wild-type allele during the first 28 days. CYP4F2 variant patients seemed to require higher doses of warfarin than those in the wild-type group; however, no significant difference in the average INR was observed (1.95 [1.14] [homozygous V433 carriers], 1.78 [0.98] [heterozygous V433M carriers], and 1.66 [0.91] [homozygous M433 carriers], P = 0.016).

IMPLICATIONS: Our study indicates that genetic variants in the Han population may enhance warfarin responsiveness, which holds clinical relevance. An increased warfarin dosage was not linked to a shorter time to therapeutic INR between CYP4F2 variant patients and those with a wild-type allele. Assessing CYP2C9 and VKORC1 genetic polymorphisms before initiating warfarin treatment in real-world practice is essential for potentially vulnerable patients and is likely to optimize therapeutic dosing.

PMID:37301690 | DOI:10.1016/j.clinthera.2023.04.006

Mult Scler Relat Disord. 2023 Jun 7;76:104799. doi: 10.1016/j.msard.2023.104799. Online ahead of print.

ABSTRACT

Multiple Sclerosis (MS) is a chronic, inflammatory, neurodegenerative disease that is characterized by a complex etiology. Efforts towards the management of MS have long been directed towards symptomatic relief, as well as the use of immune-modulatory, disease modifying therapies; however, inconsistent treatment responses still prevail, increasing the risk for disease progression. While a great deal of research attempted to unravel the complexity of treatment responses in light of epigenetic variability, parallel efforts in the direction of alternative medicine may be as paramount. Herbal compounds have long been regarded as safe and versatile options for aiding in various disorders, including neurodegenerative conditions like MS. Numerous studies have taken interest in a myriad of herbal plants for their potential benefit in alleviating some of the most common MS symptoms such as spasticity and fatigue, delaying the progression of the disease, as well as influencing the overall quality of life for MS patients. This review aims to provide a comprehensive overview of recent clinical studies examining the effects of various herbal plants on different aspects of MS, in an attempt to shed light on an important tool for aiding in the management of this complex and multifactorial disease.

PMID:37300922 | DOI:10.1016/j.msard.2023.104799

Clin Pharmacokinet. 2023 Jun 10. doi: 10.1007/s40262-023-01265-z. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: High variability in vancomycin exposure in neonates requires advanced individualized dosing regimens. Achieving steady-state trough concentration (C0) and steady-state area-under-curve (AUC0-24) targets is important to optimize treatment. The objective was to evaluate whether machine learning (ML) can be used to predict these treatment targets to calculate optimal individual dosing regimens under intermittent administration conditions.

METHODS: C0 were retrieved from a large neonatal vancomycin dataset. Individual estimates of AUC0-24 were obtained from Bayesian post hoc estimation. Various ML algorithms were used for model building to C0 and AUC0-24. An external dataset was used for predictive performance evaluation.

RESULTS: Before starting treatment, C0 can be predicted a priori using the Catboost-based C0-ML model combined with dosing regimen and nine covariates. External validation results showed a 42.5% improvement in prediction accuracy by using the ML model compared with the population pharmacokinetic model. The virtual trial showed that using the ML optimized dose; 80.3% of the virtual neonates achieved the pharmacodynamic target (C0 in the range of 10-20 mg/L), much higher than the international standard dose (37.7-61.5%). Once therapeutic drug monitoring (TDM) measurements (C0) in patients have been obtained, AUC0-24 can be further predicted using the Catboost-based AUC-ML model combined with C0 and nine covariates. External validation results showed that the AUC-ML model can achieve an prediction accuracy of 80.3%.

CONCLUSION: C0-based and AUC0-24-based ML models were developed accurately and precisely. These can be used for individual dose recommendations of vancomycin in neonates before treatment and dose revision after the first TDM result is obtained, respectively.

PMID:37300630 | DOI:10.1007/s40262-023-01265-z

J Anal Toxicol. 2023 Jun 10:bkad032. doi: 10.1093/jat/bkad032. Online ahead of print.

ABSTRACT

A middle-aged woman was found dead with multiple empty blisters of midazolam (DORMICUM®), equivalent to 450mg, near her body. The autopsy revealed that the cause of death was secondary to an asphyxia syndrome. Standard toxicological procedures identified midazolam only in blood, urine and gastric content. A quantitative analytical method for midazolam (MDZ) and 1-hydroxy-midazolam (1-OH-MDZ) was validated using protein precipitation, a phospholipid removal Ostro® plates and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). MDZ and 1-OH-MDZ were quantified in peripheral blood at 910 ng/mL and 534 ng/mL, respectively, and superior to 2000 ng/mL in urine. Reported to the body weight, the dose, which was lethal, was estimated to 6.7 mg/kg. The usual dose used in intensive care unit is 0.03-0.3 mg/kg. MDZ intoxication outside of hospital are rare given the restricted availably of this drug in France. Nevertheless, MDZ under oral form remains available in several countries. Toxic MDZ blood concentrations are described after intravenous administration for anesthesia and are not suited for oral intoxication. Based on the autopsy findings, police investigation and toxicology results, the cause of death was determined to be a self-inflicted oral MDZ acute intoxication, which is the first to be documented to the best of our knowledge. This fatal intoxication provides analytical data that could support subsequent toxicological result interpretation in similar forensic cases.

PMID:37300548 | DOI:10.1093/jat/bkad032

Int J Mol Sci. 2023 May 31;24(11):9580. doi: 10.3390/ijms24119580.

ABSTRACT

Two groups of facts have been established in previous drug development studies of the non-benzodiazepine anxiolytic fabomotizole. First, fabomotizole prevents stress-induced decrease in binding ability of the GABAA receptor's benzodiazepine site. Second, fabomotizole is a Sigma1R chaperone agonist, and exposure to Sigma1R antagonists blocks its anxiolytic effect. To prove our main hypothesis of Sigma1R involvement in GABAA receptor-dependent pharmacological effects, we performed a series of experiments on BALB/c and ICR mice using Sigma1R ligands to study anxiolytic effects of benzodiazepine tranquilizers diazepam (1 mg/kg i.p.) and phenazepam (0.1 mg/kg i.p.) in the elevated plus maze test, the anticonvulsant effects of diazepam (1 mg/kg i.p.) in the pentylenetetrazole-induced seizure model, and the hypnotic effects of pentobarbital (50 mg/kg i.p.). Sigma1R antagonists BD-1047 (1, 10, and 20 mg/kg i.p.), NE-100 (1 and 3 mg/kg i.p.), and Sigma1R agonist PRE-084 (1, 5, and 20 mg/kg i.p.) were used in the experiments. Sigma1R antagonists have been found to attenuate while Sigma1R agonists can enhance GABAARs-dependent pharmacological effects.

PMID:37298532 | DOI:10.3390/ijms24119580

Int J Mol Sci. 2023 May 26;24(11):9332. doi: 10.3390/ijms24119332.

ABSTRACT

Dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1 (DAX1) is an orphan nuclear receptor encoded by the NR0B1 gene. The functional study showed that DAX1 is a physiologically significant target for EWS/FLI1-mediated oncogenesis, particularly Ewing Sarcoma (ES). In this study, a three-dimensional DAX1 structure was modeled by employing a homology modeling approach. Furthermore, the network analysis of genes involved in Ewing Sarcoma was also carried out to evaluate the association of DAX1 and other genes with ES. Moreover, a molecular docking study was carried out to check the binding profile of screened flavonoid compounds against DAX1. Therefore, 132 flavonoids were docked in the predicted active binding pocket of DAX1. Moreover, the pharmacogenomics analysis was performed for the top ten docked compounds to evaluate the ES-related gene clusters. As a result, the five best flavonoid-docked complexes were selected and further evaluated by Molecular Dynamics (MD) simulation studies at 100 ns. The MD simulation trajectories were evaluated by generating RMSD, hydrogen bond plot analysis, and interaction energy graphs. Our results demonstrate that flavonoids showed interactive profiles in the active region of DAX1 and can be used as potential therapeutic agents against DAX1-mediated augmentation of ES after in-vitro and in-vivo evaluations.

PMID:37298283 | DOI:10.3390/ijms24119332

Int J Mol Sci. 2023 May 23;24(11):9153. doi: 10.3390/ijms24119153.

ABSTRACT

Nuclear receptors (NRs) are a vital superfamily of transcription factors that play crucial roles in physiology and pharmacology [...].

PMID:37298107 | DOI:10.3390/ijms24119153

Front Allergy. 2023 May 24;4:1214914. doi: 10.3389/falgy.2023.1214914. eCollection 2023.

NO ABSTRACT

PMID:37292091 | PMC:PMC10246496 | DOI:10.3389/falgy.2023.1214914

Clin Transl Sci. 2023 Jun 8. doi: 10.1111/cts.13520. Online ahead of print.

ABSTRACT

Globally, tuberculosis (TB) is the second most lethal infectious disease. However, in sub-Saharan Africa, TB has the largest disease burden, with drug-resistant TB increasingly becoming a concern. The social and economic impact of TB should not be overlooked, especially in areas where healthcare systems are overburdened, and resources need to be allocated judiciously. The aim of pharmacogenetics (PGx) is to improve therapeutic response and to minimize adverse drug reactions by selecting the most optimal drug and dosage for the individual patient. Implementation of PGx into routine clinical care has been slow, especially in resource-limited settings, because of perceived high costs relative to uncertain benefit. Given the impact of TB on the disease and disability burden in these regions, a better understanding and optimization of TB treatment in understudied African populations is vital. The first weeks of treatment are the most crucial for treatment success, and a point-of-care pre-emptive PGx test could start patients on the most bactericidal and least toxic drug combination. This may potentially reduce the number of patients returning to clinical care and streamline the use of limited resources across the healthcare system. This review explores the status of TB PGx in Africa, the utility of existing TB PGx testing panels, and the economic feasibility in developing a clinically valuable, cost-effective, pre-emptive PGx test to guide optimized, new dosing regimens specifically for African population groups. TB is a disease of poverty, but investment in PGx research in African populations could ensure improved treatments and long-term cost savings.

PMID:37291686 | DOI:10.1111/cts.13520

Biomed Pharmacother. 2023 Jun 6;164:114974. doi: 10.1016/j.biopha.2023.114974. Online ahead of print.

ABSTRACT

BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare disease, but it is one of the most common inflammatory neuropathies in the population. It is particularly common among patients with diabetes mellitus. This raises many problems, both with the differential diagnosis of diabetic and inflammatory neuropathy, as well as the choice of treatment. Intravenous immunoglobulin (IVIG) is one of the therapeutic options. There is evidence for the effectiveness of IVIG in treating about two-thirds of patients. However, no review has been published to date systematising studies evaluating the response to IVIG treatment in patients with CIDP and coexisting diabetes.

METHODS: The present study is based on the PRISMA statement and is registered at PROSPERO (CRD42022356180). The study included searches of the databases of MEDLINE, ERIC, CINAHL Complete, Academic Search Ultimate and Health Source: Nursing/Academic Edition, finally including seven original papers evaluating a total of 534 patients in the review. The main inclusion criteria were the presence of a group of patients with CIDP and comorbid diabetes in the study.

RESULTS: The systematic review showed a lower efficacy of IVIG treatment among patients with coexisting diabetes compared with idiopathic CIDP (61 % vs 71 %). In addition, the presence of conduction blocks on neurography and shorter disease duration proved to be significant factors improving response to treatment.

CONCLUSIONS: Current scientific data do not allow for strong recommendations on the choice of treatment for CIDP. A randomised, multicentre study evaluating the efficacy of different therapeutic approaches to this disease entity needs to be planned.

PMID:37290187 | DOI:10.1016/j.biopha.2023.114974

Int J Clin Pharm. 2023 Jun 8. doi: 10.1007/s11096-023-01608-7. Online ahead of print.

ABSTRACT

BACKGROUND: Daratumumab and isatuximab are anti-CD38 monoclonal antibodies indicated for the treatment of multiple myeloma. These agents can increase the risk of infectious complications, including viral infections. Cases of hepatitis B virus (HBV) reactivation have been reported in the literature in patients receiving anti-CD38 monoclonal antibody-based therapies.

AIM: The objective of this analysis was to determine if the association between anti-CD38 monoclonal antibody exposure and the development of hepatitis B reactivation had a detectable reporting signal in the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).

METHOD: We conducted a post marketing pharmacovigilance analysis by querying the FAERS for reports of HBV reactivation with daratumumab or isatuximab exposure reported between 2015 and 2022. Disproportionality signal analysis was conducted by calculating reporting odds ratios (RORs).

RESULTS: Sixteen cases of hepatitis B virus reactivation were reported in the FAERS database among patients receiving daratumumab or isatuximab reported between 2015 and 2022. The ROR for HBV reactivation was statistically significant for both daratumumab (ROR 4.76, 95% CI 2.76-8.22) and isatuximab (ROR 9.31, 95% CI 3.00-28.92).

CONCLUSION: Overall, our analysis demonstrates a significant reporting signal for HBV reactivation with daratumumab and isatuximab.

PMID:37289318 | DOI:10.1007/s11096-023-01608-7

Am J Pharm Educ. 2023 May;87(5):100007. doi: 10.1016/j.ajpe.2022.10.001. Epub 2023 Mar 15.

ABSTRACT

As genomic medicine becomes increasingly complex, pharmacists need to work collaboratively with other healthcare professionals to provide genomics-based care. The core pharmacist competencies in genomics were recently updated and mapped to the entrustable professional activities (EPAs). The new competency that is mapped to the "Interprofessional Team Member" EPA domain emphasizes the role of pharmacists as the pharmacogenomics experts in an interprofessional healthcare team. Interprofessional education (IPE) activities involving student pharmacists and students from other healthcare disciplines are crucial to prepare student pharmacists for a team-based approach to patient-centered care. This commentary discusses the pharmacogenomics-focused IPE activities implemented by 3 programs, the challenges faced, and the lessons learned. It also discusses strategies to develop pharmacogenomics-focused IPE activities based on existing resources. Developing pharmacogenomics-focused IPE activities will help prepare pharmacy graduates with the knowledge, skills, and attitudes to lead collaborative, interprofessional teams in the provision of pharmacogenomics-based care, consistent with the standards described in the genomics competencies for pharmacists.

PMID:37288681 | DOI:10.1016/j.ajpe.2022.10.001

Front Endocrinol (Lausanne). 2023 May 23;14:1156680. doi: 10.3389/fendo.2023.1156680. eCollection 2023.

ABSTRACT

CONTEXT: Recent evidence support that androgens play an important role in the etiology of endometrial cancer (EC). Adrenal-derived 11-oxygenated androgens are highly potent agonists of the androgen receptor (AR), comparable to testosterone (T) and dihydrotestosterone (DHT) that have not been studied in the context of EC.

METHODOLOGY: We studied a cohort of 272 newly diagnosed postmenopausal EC cases undergoing surgical treatment. Circulating concentrations of seven 11-oxygenated androgens including precursors, potent androgens and their metabolites were established in serum samples collected before and 1 month after surgery using a validated liquid chromatography tandem mass spectrometry method (LC-MS/MS). Free (unconjugated) and total (free + sulfate and glucuronide conjugates following enzymatic hydrolysis) were analyzed in relation to clinicopathological features, recurrence and disease-free survival (DFS).

RESULTS: Levels of 11-oxygenated androgens were weakly correlated to those of canonical androgens such as testosterone (T) and dihydrotestosterone (DHT), with no evidence of their association with clinicopathological features. Levels of 11-oxygenated androgens declined after surgery but remained higher in overweight and obese compared to normal weight cases. Higher levels of preoperative free 11-ketoandrosterone (11KAST) were associated with an increased risk of recurrence (Hazard ratio (HR) of 2.99 (95%CI=1.09-8.18); P=0.03). Postoperative free 11β-hydroxyandrosterone (11OHAST) levels were adversely associated with recurrence and DFS (HR = 3.23 (1.11-9.40); P=0.03 and 3.27 (1.34-8.00); P=0.009, respectively).

CONCLUSION: 11-oxygenated androgen metabolites emerge as potential prognostic markers of EC.

PMID:37288302 | PMC:PMC10242140 | DOI:10.3389/fendo.2023.1156680

Paediatr Child Health. 2023 Jun 6;28(4):205-251. doi: 10.1093/pch/pxad002. eCollection 2023 Jul.

ABSTRACT

The past two decades have seen enormous advancements in medical knowledge around the role of genetic factors of variability, both in human disease and drug response. This knowledge is increasingly being translated into guidelines that inform drug dosing, monitoring for efficacy and safety, and determining the suitability of specific agents to treat patients. Health Canada and the U.S. Food and Drug Administration have recommended using genetic information to guide dosing for more than 20 drugs. There are no current, comprehensive paediatric guidelines to assist health care professionals in the use of genetics to inform medication dosing, safety, and efficacy in children, and such guidance is urgently needed. This statement helps to guide clinician understanding of the role of pharmacogenetics and how to use this information when prescribing medications in paediatrics.

PMID:37287477 | PMC:PMC10243977 | DOI:10.1093/pch/pxad002

Paediatr Child Health. 2023 Jun 6;28(4):205-245. doi: 10.1093/pch/pxad003. eCollection 2023 Jul.

ABSTRACT

In the past decade, there have been tremendous advancements in the field of genomics that have led to significant progress in redefining the concept of precision medicine. Pharmacogenetics (PGx) is one of the most promising areas of precision medicine and is the 'low hanging fruit' of this individualized approach to medication dosing and selection. Although a variety of regulatory health agencies and professional consortia have established PGx clinical practice guidelines, implementation has been slow given numerous barriers faced by health care professionals. Many lack the training needed to interpret PGx and there are no paediatric specific guidelines. As the field of PGx continues to grow, an emphasis on collaborative inter-professional education, coupled with ongoing efforts to increase accessibility to advancing testing technology are necessary to translate this branch of precision medicine from the bench to the bedside.

PMID:37287475 | PMC:PMC10243970 | DOI:10.1093/pch/pxad003

Hum Genomics. 2023 Jun 7;17(1):51. doi: 10.1186/s40246-023-00495-3.

ABSTRACT

BACKGROUND: Cardiovascular diseases and especially Acute Coronary Syndrome (ACS) constitute a major health issue impacting millions of patients worldwide. Being a leading cause of death and hospital admissions in many European countries including Spain, it accounts for enormous amounts of healthcare expenditures for its management. Clopidogrel is one of the oldest antiplatelet medications used as standard of care in ACS.

METHODS: In this study, we performed an economic evaluation study to estimate whether a genome-guided clopidogrel treatment is cost-effective compared to conventional one in a large cohort of 243 individuals of Spanish origin suffering from ACS and treated with clopidogrel. Data were derived from the U-PGx PREPARE clinical trial. Effectiveness was measured as survival of individuals while study data on safety and efficacy, as well as on resource utilization associated with each adverse drug reaction were used to measure costs to treat these adverse drug reactions. A generalized linear regression model was used to estimate cost differences for both study groups.

RESULTS: Based on our findings, PGx-guided treatment group is cost-effective. PGx-guided treatment demonstrated to have 50% less hospital admissions, reduced emergency visits and almost 13% less ADRs compared to the non-PGx approach with mean QALY 1.07 (95% CI, 1.04-1.10) versus 1.06 (95% CI, 1.03-1.09) for the control group, while life years for both groups were 1.24 (95% CI, 1.20-1.26) and 1.23 (95% CI, 1.19-1.26), respectively. The mean total cost of PGx-guided treatment was 50% less expensive than conventional therapy with clopidogrel [€883 (95% UI, €316-€1582), compared to €1,755 (95% UI, €765-€2949)].

CONCLUSION: These findings suggest that PGx-guided clopidogrel treatment represents a cost-effective option for patients suffering from ACS in the Spanish healthcare setting.

PMID:37287029 | DOI:10.1186/s40246-023-00495-3

Front Pharmacol. 2023 May 22;14:1180640. doi: 10.3389/fphar.2023.1180640. eCollection 2023.

ABSTRACT

Background: Population genomic studies of individuals of Indigenous ancestry have been extremely limited comprising <0.5% of participants in international genetic databases and genome-wide association studies, contributing to a "genomic gap" that limits their access to personalised medicine. While Indigenous Australians face a high burden of chronic disease and associated medication exposure, corresponding genomic and drug safety datasets are sorely lacking. Methods: To address this, we conducted a pharmacogenomic study of almost 500 individuals from a founder Indigenous Tiwi population. Whole genome sequencing was performed using short-read Illumina Novaseq6000 technology. We characterised the pharmacogenomics (PGx) landscape of this population by analysing sequencing results and associated pharmacological treatment data. Results: We observed that every individual in the cohort carry at least one actionable genotype and 77% of them carry at least three clinically actionable genotypes across 19 pharmacogenes. Overall, 41% of the Tiwi cohort were predicted to exhibit impaired CYP2D6 metabolism, with this frequency being much higher than that for other global populations. Over half of the population predicted an impaired CYP2C9, CYP2C19, and CYP2B6 metabolism with implications for the processing of commonly used analgesics, statins, anticoagulants, antiretrovirals, antidepressants, and antipsychotics. Moreover, we identified 31 potentially actionable novel variants within Very Important Pharmacogenes (VIPs), five of which were common among the Tiwi. We further detected important clinical implications for the drugs involved with cancer pharmacogenomics such as thiopurines and tamoxifen, immunosuppressants like tacrolimus and certain antivirals used in the hepatitis C treatment due to potential differences in their metabolic processing. Conclusion: The pharmacogenomic profiles generated in our study demonstrate the utility of pre-emptive PGx testing and have the potential to help guide the development and application of precision therapeutic strategies tailored to Tiwi Indigenous patients. Our research provides valuable insights on pre-emptive PGx testing and the feasibility of its use in ancestrally diverse populations, emphasizing the need for increased diversity and inclusivity in PGx investigations.

PMID:37284308 | PMC:PMC10241071 | DOI:10.3389/fphar.2023.1180640

Talanta. 2023 Nov 1;264:124692. doi: 10.1016/j.talanta.2023.124692. Epub 2023 Jun 1.

ABSTRACT

Cardiovascular diseases are among the major causes of mortality and morbidity. Warfarin is often prescribed for these disorders, an anticoagulant with inter and intra-dosage variability dose required to achieve the target international normalized ratio. Warfarin presents a narrow therapeutic index, and due to its variability, it can often be associated with the risk of hemorrhage, or in other patients, thromboembolism. Single-nucleotide polymorphisms are included in the causes that contribute to this variability. The Cytochrome P450 (CYP) 2C9*3 genetic polymorphism modifies its enzymatic activity, and hence warfarin's plasmatic concentration. Thus, the need for a selective, rapid, low-cost, and real-time detection device is crucial before prescribing warfarin. In this work, a disposable electrochemical DNA-based biosensor capable of detecting CYP2C9*3 polymorphism was developed. By analyzing genomic databases, two specific 78 base pairs DNA probes; one with the wild-type adenine (Target-A) and another with the cytosine (Target-C) single-nucleotide genetic variation were designed. The biosensor implied the immobilization on screen-printed gold electrodes of a self-assembled monolayer composed by mercaptohexanol and a linear CYP2C9*3 DNA-capture probe. To improve the selectivity and avoid secondary structures a sandwich format of the CYP2C9*3 allele was designed using complementary fluorescein isothiocyanate-labeled signaling DNA probe and enzymatic amplification of the electrochemical signal. Chronoamperometric measurements were performed at a range of 0.015-1.00 nM for both DNA targets achieving limit of detection of 42 p.m. The developed DNA-based biosensor was able to discriminate between the two synthetic target DNA targets, as well as the targeted denatured genomic DNA, extracted from volunteers genotyped as non-variant homozygous (A/A) and heterozygous (A/C) of the CYP2C9*3 polymorphism.

PMID:37276677 | DOI:10.1016/j.talanta.2023.124692

J Immunother Cancer. 2023 Jun;11(6):e007255. doi: 10.1136/jitc-2023-007255.

NO ABSTRACT

PMID:37277194 | DOI:10.1136/jitc-2023-007255

Ann Intern Med. 2023 Jun 6. doi: 10.7326/J23-0031. Online ahead of print.

ABSTRACT

Swen JJ, van der Wouden CH, Manson LE, et al; Ubiquitous Pharmacogenetics Consortium. A 12-gene pharmacogenetic panel to prevent adverse drug reactions: an open-label, multicentre, controlled, cluster-randomised crossover implementation study. Lancet. 2023;401:347-356. 36739136.

PMID:37276599 | DOI:10.7326/J23-0031