Disposition of Oral Cannabidiol-Rich Cannabis Extracts in Children with Epilepsy.

Clin Pharmacokinet. 2020 Feb 12;:

Authors: Wang GS, Bourne DWA, Klawitter J, Sempio C, Chapman K, Knupp K, Wempe MF, Borgelt L, Christians U, Leonard J, Heard K, Bajaj L

Abstract
BACKGROUND AND OBJECTIVES: Despite limited evidence, cannabidiol-rich cannabis extracts have been popularly used in pediatrics. With increased use, it is critical to determine basic pharmacokinetic parameters of cannabidiol in these extracts in the pediatric population. The objective of this study was to determine the disposition of oral cannabidiol cannabis extracts and drug interactions in children with pediatric epilepsy.
METHODS: We conducted a prospective observational study evaluating the disposition of oral cannabidiol in children (< 18 years of age) receiving cannabidiol extracts for epilepsy. Subjects underwent serial blood draws after oral cannabidiol administration. Cannabidiol and metabolites, along with anticonvulsant concentrations were determined.
RESULTS: Twenty-nine patients had sufficient pharmacokinetic data and were included in the analysis. Mean age was 9.7 years (standard deviation 4.3) and 17 patients (59%) were male. Median peak plasma cannabidiol concentrations was 13.1 ng/mL (interquartile range 6.8-39.3 ng mL); median time to peak of 2.0 h (interquartile range 2.0-4.0 h). Mean acute elimination half-life of oral cannabidiol was 6.2 h (standard deviation 1.8 h). There was an observed half-life of degradation of 533 days noted for cannabidiol concentrations when stored for 0.6-3.1 years. There was some impact on cannabidiol pharmacokinetic parameters when cannabidiol was co-administered with zonisamide (elimination rate constant and V1) and levetiracetam (elimination rate constant).
CONCLUSIONS: In pediatric patients using oral cannabidiol-rich cannabis extract for epilepsy, the time to peak concentration of plasma cannabidiol and average acute elimination half-life were shorter than those reported for adults. Co-administration of zonisamide and levetiracetam had some impact on cannabidiol pharmacokinetic parameters. There was an observed degradation of plasma cannabidiol in long-term storage.
CLINICAL REGISTRATION: ClinicalTrials.gov Identifer no. NCT02447198.

PMID: 32048179 [PubMed - as supplied by publisher]

The RNA-binding protein QKI suppresses tumorigenesis of clear cell renal cell carcinoma by regulating the expression of HIF-1α.

J Cancer. 2020;11(6):1359-1370

Authors: Shi F, Wei D, Zhu Z, Yan F, Wang F, Zhang K, Li X, Zheng Y, Yuan J, Lu Z, Yuan J

Abstract
Backgrounds: A number of genetic and biological phenomena imply that tumorigenesis of clear cell renal cell carcinoma (ccRCC) is highly correlated with hypoxia-induced factor-1a (HIF-1α). Recently, research focusing on the post-transcriptional regulation of HIF-1α has provided a new perspective for ccRCC therapy. In this study, we observed the expression pattern of the RNA-binding protein QKI, which could regulate HIF expression in ccRCC both in vitro and in vivo. Methods: Tissue microarraywas subjected to immunohistochemistry and tumour cell lines and nude mice were used for in vitro and in vivo assays. QKI overexpression or knockdown was assessed in renal cancer cells. Results: The overexpression of QKI inhibited the proliferation of the 786-0 and caki-1 cells, blocked the cells' entry into the S phase, and promoted apoptosis. In ectopic-implantation nude mice model, QKI depletion significantly increased tumor sizes and initiation rates. Tissue microarrays showed that the expression of QKI genes, and especially QKI-6, was significantly decreased in tumor tissues compared with these in normal kidney tissues. Moreover, decreased QKI expression was closely correlated with high tumor grade, poor differentiation, and poor survival. Conclusions: QKI may be useful as a novel, independent diagnostic and biological marker for ccRCC.

PMID: 32047543 [PubMed]

DPD Testing Before Treatment With Fluoropyrimidines in the Amsterdam UMCs: An Evaluation of Current Pharmacogenetic Practice.

Front Pharmacol. 2019;10:1609

Authors: Martens FK, Huntjens DW, Rigter T, Bartels M, Bet PM, Cornel MC

Abstract
Introduction: The fluoropyrimidines (FP) (5-Fluorouracil, capecitabine, and tegafur) are commonly used anti-cancer drugs, but lead to moderate to severe toxicity in about 10-40% of patients. DPD testing [either the enzyme activity of dihydropyrimidine dehydrogenase (DPD) or the DPYD genotype] identifies patients at higher risk for toxicity who may be treated more safely with a lower drug dose. The Netherland's National guideline for colon carcinoma was updated in 2017 to recommend DPYD genotyping before treatment with FP. Pretreatment DPYD genotyping identifies approximately 50% of the patients that will develop severe FP toxicity. The aim of the study was to assess the uptake of DPD testing in the Amsterdam University Medical Centers over time and to evaluate stakeholder experiences to indicate barriers and facilitators of implementation in routine clinical care.
Materials and Methods: We used a mixed-method approach involving electronic patient records of 753 unique patients and pharmacy information systems analyses and fifteen semi-structured interviews with oncologists, pharmacists, and patients. The constellation perspective was used to identify barriers and facilitators at the level of practice, culture and structure. The proportion of FP users who were DPD tested pretreatment showed an increase from 1% (1/86) in Q2-2017 up to 87% (73/84) in Q4-2018. Unlike a landmark paper published in 2015, the National guideline for colorectal carcinoma followed by meetings to achieve local consensus led to this steep increase in the proportion of patients tested.
Results: Facilitating factors for stakeholders to implement testing included the existence of clear protocols, (anecdotal) evidence of the utility, being aware that peers are adhering to standard practice and clear and simple procedures for ordering and reporting. Main barriers included the lack of clear divisions of responsibilities, the lack of consensus on a test approach, long turn-around times and non-user-friendly IT-infrastructures. More professional education on the utility and limitations of pharmacogenetic testing was desired by most stakeholders.
Conclusion: While the evidence for DPD testing was sufficient, only after the update of a National guideline and local consensus meetings the proportion of FP users that were DPD tested pretreatment rose to 87%. The implementation of personalized medicine requires stakeholders involved to attune practice, culture and structure.

PMID: 32047438 [PubMed]

Alternative promoters control UGT2B17-dependent androgen catabolism in prostate cancer and its influence on progression.

Br J Cancer. 2020 Feb 12;:

Authors: Lévesque E, Labriet A, Hovington H, Allain ÉP, Melo-Garcia L, Rouleau M, Brisson H, Turcotte V, Caron P, Villeneuve L, Leclercq M, Droit A, Audet-Walsh E, Simonyan D, Fradet Y, Lacombe L, Guillemette C

Abstract
BACKGROUND: Perturbation of the major UGT2B17-dependent androgen catabolism pathway has the potential to affect prostate cancer (PCa) progression. The objective was to evaluate UGT2B17 protein expression in primary tumours in relation to hormone levels, disease characteristics and cancer evolution.
METHODS: We conducted an analysis of a high-density prostate tumour tissue microarray consisting of 239 localised PCa cases treated by radical prostatectomy (RP). Cox proportional hazard ratio analysis was used to evaluate biochemical recurrence (BCR), and a linear regression model evaluated variations in circulating hormone levels measured by mass spectrometry. The transcriptome of UGT2B17 in PCa was established by using RNA-sequencing data.
RESULTS: UGT2B17 expression in primary tumours was associated with node-positive disease at RP and linked to circulating levels of 3α-diol-17 glucuronide, a major circulating DHT metabolite produced by the UGT2B17 pathway. UGT2B17 was an independent prognostic factor linked to BCR after RP, and its overexpression was associated with development of metastasis. Finally, we demonstrated that distinctive alternative promoters dictate UGT2B17-dependent androgen catabolism in localised and metastatic PCa.
CONCLUSIONS: The androgen-inactivating gene UGT2B17 is controlled by overlooked regulatory regions in PCa. UGT2B17 expression in primary tumours influences the steroidome, and is associated with relevant clinical outcomes, such as BCR and metastasis.

PMID: 32047296 [PubMed - as supplied by publisher]

Emerging roles for UDP-glucuronosyltransferases in drug resistance and cancer progression.

Br J Cancer. 2020 Feb 12;:

Authors: Allain EP, Rouleau M, Lévesque E, Guillemette C

Abstract
The best-known role of UDP-glucuronosyltransferase enzymes (UGTs) in cancer is the metabolic inactivation of drug therapies. By conjugating glucuronic acid to lipophilic drugs, UGTs impair the biological activity and enhance the water solubility of these agents, driving their elimination. Multiple clinical observations support an expanding role for UGTs as modulators of the drug response and in mediating drug resistance in numerous cancer types. However, accumulating evidence also suggests an influence of the UGT pathway on cancer progression. Dysregulation of the expression and activity of UGTs has been associated with the progression of several cancers, arguing for UGTs as possible mediators of oncogenic pathways and/or disease accelerators in a drug-naive context. The consequences of altered UGT activity on tumour biology are incompletely understood. They might be associated with perturbed levels of bioactive endogenous metabolites such as steroids and bioactive lipids that are inactivated by UGTs or through non-enzymatic mechanisms, thereby eliciting oncogenic signalling cascades. This review highlights the evidence supporting dual roles for the UGT pathway, affecting cancer progression and drug resistance. Pharmacogenomic testing of UGT profiles in patients and the development of therapeutic options that impair UGT actions could provide useful prognostic and predictive biomarkers and enhance the efficacy of anti-cancer drugs.

PMID: 32047295 [PubMed - as supplied by publisher]

Staphylococcal species less frequently isolated from human clinical specimens - are they a threat for hospital patients?

BMC Infect Dis. 2020 Feb 11;20(1):128

Authors: Szemraj M, Grazul M, Balcerczak E, Szewczyk EM

Abstract
BACKGROUND: Coagulase-negative staphylococci belonging to S. haemolyticus, S. hominis subsp. hominis, S. simulans, and S. warneri are often described as etiological factors of infections. Staphylococci are a phylogenetically coherent group; nevertheless, there are differences among the species which may be important to clinicians.
METHODS: We investigated selected virulence factors and antibiotic resistance that were phenotypically demonstrated, the presence and expression of genes encoding the virulence factors, and the type of the SCCmec cassette.
RESULTS: The differences between the tested species were revealed. A great number of isolates produced a biofilm and many of them contained single icaADBC operon genes. Clear differences between species in the lipolytic activity spectrum could be related to their ability to cause various types of infections. Our studies also revealed the presence of genes encoding virulence factors homologous to S. aureus in the analysed species such as enterotoxin and pvl genes, which were also expressed in single isolates of S. simulans and S. warneri. S. haemolyticus and S. hominis subsp. hominis isolates were resistant to all clinically important antibiotics including ß-lactams. The identified SCCmec cassettes belonged to IV, V, VII, and IX type but most of the detected cassettes were non-typeable. Among the investigated species, S. hominis subsp. hominis isolates accumulated virulence genes typical for S. aureus in the most efficient way and were widely resistant to antibiotics.
CONCLUSIONS: Our results clearly indicated significant differences between the tested species, which might be a result of the horizontal gene transfer (HGT) and can lead to the formation and selection of multi-drug resistant strains as well as strains with new virulence features. Such strains can have a new clinical relevance.

PMID: 32046678 [PubMed - in process]

Precision Medicine in Non-Communicable Diseases.

High Throughput. 2020 Feb 07;9(1):

Authors: Novelli G, Biancolella M, Latini A, Spallone A, Borgiani P, Papaluca M

Abstract
The increase in life expectancy during the 20th century ranks as one of society's greatest achievements, with massive growth in the numbers and proportion of the elderly, virtually occurring in every country of the world. The burden of chronic diseases is one of the main consequences of this phenomenon, severely hampering the quality of life of elderly people and challenging the efficiency and sustainability of healthcare systems. Non-communicable diseases (NCDs) are considered a global emergency responsible for over 70% of deaths worldwide. NCDs are also the basis for complex and multifactorial diseases such as hypertension, diabetes, and obesity. The epidemics of NCDs are a consequence of a complex interaction between health, economic growth, and development. This interaction includes the individual genome, the microbiome, the metabolome, the immune status, and environmental factors such as nutritional and chemical exposure. To counteract NCDs, it is therefore essential to develop an innovative, personalized, preventative, early care model through the integration of different molecular profiles of individuals to identify both the critical biomarkers of NCD susceptibility and to discover novel therapeutic targets.

PMID: 32046063 [PubMed]

11 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

pharmacogenomics

These pubmed results were generated on 2020/02/12

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Evaluation of gefitinib systemic exposure in EGFR-mutated non-small cell lung cancer patients with gefitinib-induced severe hepatotoxicity.

Cancer Chemother Pharmacol. 2020 Feb 10;:

Authors: Kawamura T, Imamura CK, Kenmotsu H, Taira T, Omori S, Nakashima K, Wakuda K, Ono A, Naito T, Murakami H, Mushiroda T, Takahashi T, Tanigawara Y

Abstract
PURPOSE: Severe hepatotoxicity induced by the standard dose of gefitinib (250 mg daily) often becomes manageable by dose reduction to 250 mg every other day. Thus, we hypothesized that systemic exposure of standard-dose gefitinib in patients with experience of severe hepatotoxicity might be higher than that in patients without severe hepatotoxicity.
METHODS: Patients with advanced epidermal growth factor receptor-mutated non-small cell lung cancer who were receiving gefitinib either at a reduced dose (250 mg every other day) because of intolerable severe toxicity or at a standard dose (250 mg daily) were enrolled. A series of blood samples were collected to estimate pharmacokinetic parameters and calculate systemic exposure of standard-dose gefitinib (area under the concentration-time curve from 0 to 24 h at steady state, AUC0-24,ss). Systemic exposure of unbound gefitinib (fu·AUC0-24,ss) was also assessed, because gefitinib is extensively bound to serum proteins.
RESULTS: Of the 38 enrolled patients, 34 (23 patients without experience of severe hepatotoxicity, 11 patients with experience of severe hepatotoxicity) were evaluable. There was no significant differences in total AUC0-24,ss or unbound fu·AUC0-24,ss between patients with and without experience of severe hepatotoxicity. Analysis of the time to severe hepatotoxicity indicated no difference between patients with a high AUC0-24,ss and those with a low AUC0-24,ss of either total or unbound gefitinib.
CONCLUSION: This study suggests that reversible severe hepatotoxicity is not caused by high systemic exposure of gefitinib.

PMID: 32040702 [PubMed - as supplied by publisher]

Focus group testing of a mobile app for pharmacogenetic-guided dosing.

J Am Assoc Nurse Pract. 2020 Feb 04;:

Authors: Dodson CH, Baker E

Abstract
BACKGROUND: A common barrier to implementation of precision medicine is the lack of use of published clinical practice guidelines. Consequently, a user-friendly mechanism to easily adopt these guidelines is imperative.
PURPOSE: The purpose of this study was to evaluate the perceptions of a prototype of a clinical decision support tool through a mobile application for pharmacogenetics.
METHODOLOGICAL ORIENTATION: A case study on a patient requiring pharmacogenetic testing was provided to the participants. The participants were given up to 30 minutes to identify the correct dosing in the clinical decision support tool based on clinical evidence-based guidelines. Immediately after the utilization of the mobile app, focus group interviews were conducted to identify the perceptions of the tool, obstacles associated with the tool, and suggestions for improvement of the tool.
SAMPLE: Focus group interviews with 23 nurse practitioners and nurse practitioner students were conducted. Field notes and audio recordings were taken.
CONCLUSIONS: Specific feedback for improvement in the font and size of text, color contrast, use of drug calculator, automatic input, and desire for further development of education portal were found within the data. The findings revealed useful feedback to adjust the prototype to improve the ease of use among nurse practitioners.
IMPLICATIONS FOR PRACTICE: The revision of this mobile app will improve user friendliness to increase applicability within health care. The mobile app can be used for future research to identify improvements in patient outcomes after implementing this tool.

PMID: 32039960 [PubMed - as supplied by publisher]

Machine Learning Algorithm for Predicting Warfarin Dose in Caribbean Hispanics Using Pharmacogenetic Data.

Front Pharmacol. 2019;10:1550

Authors: Roche-Lima A, Roman-Santiago A, Feliu-Maldonado R, Rodriguez-Maldonado J, Nieves-Rodriguez BG, Carrasquillo-Carrion K, Ramos CM, da Luz Sant'Ana I, Massey SE, Duconge J

Abstract
Despite some previous examples of successful application to the field of pharmacogenomics, the utility of machine learning (ML) techniques for warfarin dose predictions in Caribbean Hispanic patients has yet to be fully evaluated. This study compares seven ML methods to predict warfarin dosing in Caribbean Hispanics. This is a secondary analysis of genetic and non-genetic clinical data from 190 cardiovascular Hispanic patients. Seven ML algorithms were applied to the data. Data was divided into 80 and 20% to be used as training and test sets. ML algorithms were trained with the training set to obtain the models. Model performance was determined by computing the corresponding mean absolute error (MAE) and % patients whose predicted optimal dose were within ±20% of the actual stabilization dose, and then compared between groups of patients with "normal" (i.e., > 21 but <49 mg/week), low (i.e., ≤21 mg/week, "sensitive"), and high (i.e., ≥49 mg/week, "resistant") dose requirements. Random forest regression (RFR) significantly outperform all other methods, with a MAE of 4.73 mg/week and 80.56% of cases within ±20% of the actual stabilization dose. Among those with "normal" dose requirements, RFR performance is also better than the rest of models (MAE = 2.91 mg/week). In the "sensitive" group, support vector regression (SVR) shows superiority over the others with lower MAE of 4.79 mg/week. Finally, multivariate adaptive splines (MARS) shows the best performance in the resistant group (MAE = 7.22 mg/week) and 66.7% of predictions within ±20%. Models generated by using RFR, MARS, and SVR algorithms showed significantly better predictions of weekly warfarin dosing in the studied cohorts than other algorithms. Better performance of the ML models for patients with "normal," "sensitive," and "resistant" to warfarin were obtained when compared to other populations and previous statistical models.

PMID: 32038238 [PubMed]

Effect of Gene-Based Warfarin Dosing on Anticoagulation Control and Clinical Events in a Real-World Setting.

Front Pharmacol. 2019;10:1527

Authors: Zhang J, Wu T, Chen W, Fu J, Xia X, Chen L

Abstract
The cytochrome P450 2C9 and vitamin K epoxide reductase complex subunit 1 genotypes are associated with anticoagulation control and the clinical events in warfarin therapy. However, the clinical utility of gene-based warfarin dosing (GBWD) is controversial. We compared the anticoagulation control and clinical events related to warfarin with GBWD to those with clinically fixed dosing (CFD). A retrospective cohort study was conducted in a real-world setting. Of the 915 patients who were reviewed, 844 patients met the study-entry criteria; 413 cases were guided by GBWD using the International Warfarin Pharmacogenetic Consortium algorithm; 431 cases were guided by CFD (2.5 mg/day). The primary outcomes were the time needed to achieve the therapeutic International Normalized Ratio (INR) and the time in the therapeutic range (TTR) during a 3-month timeframe. The time needed to achieve the therapeutic INR (in days) for patients in the GBWD group was shorter than that for patients in the CFD group (10.21 ± 4.68 vs. 14.31 ± 8.26, P < 0.001). The overall TTR (Day 4-90) was significantly different between the GBWD group and CFD group (56.86 ± 10.72 vs. 52.87 ± 13.92, P = 0.007).In subgroup analysis, the TTR was also significantly different between the GBWD group and CFD group during the first month of treatment (Day 4-14: 54.28 ± 21.90 vs. 47.01 ± 26.25, P = 0.012; Day 15-28: 59.60 ± 20.12 vs. 51.71 ± 18.96, P = 0.001). However, no significant difference in the TTR was observed after 29 days of treatment. These data suggest that GBWD provided clinical benefits.

PMID: 32038232 [PubMed]

CYP2D6 genotyping analysis and functional characterization of novel allelic variants in a Ni-Vanuatu and Kenyan population by assessing dextromethorphan O-demethylation activity.

Drug Metab Pharmacokinet. 2019 Jul 20;:

Authors: Gutiérrez Rico EM, Kikuchi A, Saito T, Kumondai M, Hishinuma E, Kaneko A, Chan CW, Gitaka J, Nakayoshi T, Oda A, Saito S, Hirasawa N, Hiratsuka M

Abstract
While CYP2D6 allele and phenotype frequencies have been extensively studied, currently, very little ethnically specific data is available regarding the East African and South Pacific region, including Kenya and Vanuatu. The absence of information regarding gene polymorphisms and their resulting clinical effects in these populations may hinder treatment strategies and patient outcome. Given the scarceness of CYP2D6 related data in these populations, the purpose of this study was to perform a pharmacogenomic analysis of the Kenyan and Ni-Vanuatu population and ultimately characterize the enzymatic properties of eight novel CYP2D6 variant proteins expressed in 293FT cells in vitro using dextromethorphan as a substrate. Our study revealed a prevalence of functional alleles in both populations a low frequency for decreased function defining genotypes in the Ni-Vanuatu population, with approximately 36% of our Kenyan subjects presenting substrate-dependent decreased function alleles. Additionally, 6 variants (P171L, G306R, V402L, K1, K2, and K3) showed significantly reduced intrinsic clearance compared to wild-type CYP2D6.1. Our findings aid in efforts to bridge the gap between pharmacogenomic analysis and clinical application, by providing useful information in the development of ethnic-specific strategies as well as stressing the importance of population-specific genotyping when conducting multi-regional clinical trials and designing therapeutic strategies.

PMID: 32037159 [PubMed - as supplied by publisher]

Associating filaggrin copy number variation and atopic dermatitis in African-Americans: Challenges and opportunities.

J Dermatol Sci. 2020 Jan 31;:

Authors: Margolis DJ, Mitra N, Berna R, Hoffstad O, Kim BS, Yan A, Zaenglein AL, Fuxench ZC, Quiggle AM, de Guzman Strong C, Wong XFCC, Common JE

PMID: 32037100 [PubMed - as supplied by publisher]

The search for precision.

Cleve Clin J Med. 2020 02;87(2):71-72

Authors: Mandell BF

PMID: 32015054 [PubMed - indexed for MEDLINE]

The role of single strand break repair pathways in cellular responses to camptothecin induced DNA damage.

Biomed Pharmacother. 2020 Feb 06;125:109875

Authors: Mei C, Lei L, Tan LM, Xu XJ, He BM, Luo C, Yin JY, Li X, Zhang W, Zhou HH, Liu ZQ

Abstract
Efficient DNA repair is critical for cell survival following exposure to DNA topoisomerase I (Top1) inhibitors camptothecin, a nature product from which the common chemotherapeutic drugs irinotecan and topotecan are derived. The camptothecin-derived agents exert their antitumor activities by specifically stabilizing the Top1-DNA covalent complexes (Top1cc) and blocking the DNA religation step. When exposed to these DNA damage agents, tumor cells quickly activate DNA damage response. This allows sufficient time to remove the Top1ccs and prevent tumor cells from apoptosis. Several repair pathways have been implicated in this process. One of the most relevant repair modes is DNA single strand break repair (SSBR) pathway. The expression level or mutagenesis of specific repair factors involved in SSBR pathway may play an indispensable role in individual's capacity of repairing camptothecin induced DNA damage. Therefore, understanding of the tolerance pathways counteracted to camptothecin cytotoxicity is crucial in alleviating chemotherapy resistance. This review focus on the SSBR pathway in repair camptothecin induced DNA damage, aiming to provide insights into the potential molecular determinants of camptothecin chemosensitivity.

PMID: 32036211 [PubMed - as supplied by publisher]

Immunogenetics in stem cell donor registry work: The DKMS example (Part 2).

Int J Immunogenet. 2020 Feb 07;:

Authors: Schmidt AH, Sauter J, Baier DM, Daiss J, Keller A, Klussmeier A, Mengling T, Rall G, Riethmüller T, Schöfl G, Solloch UV, Torosian T, Means D, Kelly H, Jagannathan L, Paul P, Giani AS, Hildebrand S, Schumacher S, Markert J, Füssel M, Hofmann JA, Schäfer T, Pingel J, Lange V, Schetelig J

Abstract
DKMS is a leading stem cell donor registry with more than 9 million donors. Donor registry activities share many touch points with topics from immunogenetics or population genetics. In this two-part review article, we deal with these aspects of donor registry work by using the example of DKMS. In the second part of the review, we focus on donor typing of non-HLA genes, the impact of donor age, gender and CMV serostatus on donation probabilities, the identification of novel HLA, KIR and MIC alleles by high-throughput donor typing, the activities of the Collaborative Biobank and pharmacogenetics in the donor registry context.

PMID: 32034894 [PubMed - as supplied by publisher]

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

pharmacogenomics

These pubmed results were generated on 2020/02/08

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

pharmacogenomics

These pubmed results were generated on 2020/02/08

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

HLA associations with infliximab-induced liver injury.

Pharmacogenomics J. 2020 Feb 06;:

Authors: Bruno CD, Fremd B, Church RJ, Daly AK, Aithal GP, Björnsson ES, Larrey D, Watkins PB, Chow CR

Abstract
Biomarkers that are able to identify patients at risk of drug-induced liver injury (DILI) after treatment with infliximab could be important in increasing the safety of infliximab use. We performed a genetic analysis to identify possible human leukocyte antigen (HLA) associations with DILI in European Caucasian users of infliximab in a retrospective study of 16 infliximab-DILI patients and 60 matched controls. In infliximab-associated liver injury, multiple potentially causal individual HLA associations were observed, as well as possible haplotypes. The strongest associated HLA allele was HLA-B*39:01 (P = 0.001; odds ratio [OR] 43.6; 95% confidence interval [CI] 2.8-infinity), which always appeared with another associated allele C*12:03 (P = 0.032; OR 6.1; 95% CI 0.9-47.4). Other associations were observed with HLAs DQB1*02:01 (P = 0.007; OR 5.7; 95% CI 1.4-24.8), DRB1*03:01 (P = 0.012; OR 4.9; 95% CI 1.2-20.5), and B*08:01 (P = 0.048; OR 3.4; 95% CI 0.9-13.2), which also appeared together whenever present in cases. Additional associations were found with HLA-DPB1*10:01 (P = 0.042; OR 20.9; 95% CI 0.7-infinity) and HLA-DRB1*04:04 (P = 0.042; OR 20.9; 95% CI 0.7-infinity). A strong association with HLA-B*39:01 was identified as a potentially causal risk factor for infliximab-induced DILI. Future work should aim to validate this finding and explore possible mechanisms through which the biologic interacts with this particular allele.

PMID: 32024945 [PubMed - as supplied by publisher]