Abstract:
:Background: Genetic variability in some of the genes that affect absorption, distribution, metabolism, and elimination ("pharmacogenes") can significantly influence an individual's response to the drug and consequently the effectiveness of treatment and possible adverse drug events. The rapid development of sequencing methods in recent years and consequently the increased integration of next-generation sequencing technologies into the clinical settings has enabled extensive genotyping of pharmacogenes for personalized treatment. The aim of the present study was to investigate the frequency and variety of potentially actionable pharmacogenetic findings in the Slovenian population. Methods: De-identified data from diagnostic exome sequencing in 1904 cases submitted to our institution were analyzed for variants within 293 genes associated with drug response. Filtered variants were classified according to population frequency, variant type, the functional impact of the variant, pathogenicity predictions and characterization in the Pharmacogenomics Knowledgebase (PharmGKB) and ClinVar. Results: We observed a total of 24 known actionable pharmacogenetic variants (PharmGKB 1A or 1B level of evidence), comprising approximately 26 drugs, of which, 12 were rare, with the population frequency below 1%. Furthermore, we identified an additional 61 variants with PharmGKB 2A or 2B clinical annotations. We detected 308 novel/rare potentially actionable variants: 177 protein-truncating variants and 131 missense variants predicted to be pathogenic based on several pathogenicity predictions. Conclusion: In the present study, we estimated the burden of pharmacogenetic variants in nationally based exome sequencing data and investigated the potential clinical usefulness of detected findings for personalized treatment. We provide the first comprehensive overview of known pharmacogenetic variants in the Slovenian population, as well as reveal a great proportion of novel/rare variants with a potential to influence drug response.
journal_name
Front Pharmacoljournal_title
Frontiers in pharmacologyauthors
Hočevar K,Maver A,Peterlin Bdoi
10.3389/fphar.2019.00240subject
Has Abstractpub_date
2019-03-14 00:00:00pages
240issn
1663-9812journal_volume
10pub_type
杂志文章abstract::Background: Alzheimer's disease (AD), is a progressive neurodegenerative disease that is characterized by cognitive loss. Most researchers believe that aggregation and accumulation of β-amyloid peptides (Aβ) in brain cells are the central pathological hallmark of this disease. Methods: Based on the amyloid hypothesis,...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00969
更新日期:2018-01-08 00:00:00
abstract::Wear particles that detach from the surface of prostheses induce excessive activation of osteoclast and immoderate release of inflammatory cytokines that lead to peri-implant osteolysis and aseptic loosening. In this work, we investigated whether magnoflorine, a quaternary aporphine alkaloid extracted from the Chinese...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.00389
更新日期:2020-04-02 00:00:00
abstract::Clinical studies have shown that Selank had an anxiolytic effect comparable to that of classical benzodiazepine drugs, which can enhance the inhibitory effect of GABA by allosteric modulation of GABAA receptors. These data suggest that the molecular mechanism of the effect of Selank may also be related to its ability ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00089
更新日期:2017-02-28 00:00:00
abstract::Objective: To evaluate the hemostasis and coagulation effect of Hemocoagulase Bothrops Atrox in benign prostatic hyperplasia (BPH) patients undergoing transurethral bipolar plasmakinetic prostatectomy (TUPKP). Methods: This study adopted a multicenter, prospective, and real world design. BPH patients undergoing TUPKP ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.01426
更新日期:2019-11-27 00:00:00
abstract::Prostate cancer (PCa) is one of the most prevalent male cancers in western world. Radiation therapy (RT) is commonly used to treat PCa patients. However, a certain proportion of patients develop radioresistant PCa cells, which results in metastatic disease. Statins, which inhibit 3-hydroxy-3-methyl glutaryl coenzyme A...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00600
更新日期:2018-06-13 00:00:00
abstract:PURPOSE:Colostrum has been proposed to treat severe dryness and problematic eye lesions showing a beneficial effect. The aim of the study was to investigate the effect of 2-fucosyl-lactose, a natural sugar present in the human colostrum, in an experimental dry eye. METHODS:Dry eye was induced in adult male New Zealand...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2015.00280
更新日期:2015-11-18 00:00:00
abstract::The exponential growth of the Internet of Things and the global popularity and remarkable decline in cost of the mobile phone is driving the digital transformation of medical practice. The rapidly maturing digital, non-medical world of mobile (wireless) devices, cloud computing and social networking is coalescing with...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2016.00218
更新日期:2016-07-21 00:00:00
abstract::Hypertension is a prevalent, complex, and polygenic cardiovascular disease, which is associated with increased mortality and morbidity. Across the world, traditional Chinese medicine (TCM) constituted by herbal medicine and non-pharmacological therapies is used to assist blood pressure management. Though widely accept...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2019.00158
更新日期:2019-03-08 00:00:00
abstract::Marantodes pumilum (Primulaceae) has been used in Malaysian folk medicine to help women regain strength after delivery and for "sickness in the bones." It was previously revealed that its extracts inhibited xanthine oxidase (XO) activity in vitro. The leaves and roots of M. pumilum var. alata (MPA), var. pumila (MPP),...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.00289
更新日期:2020-03-17 00:00:00
abstract::Phenethyl isothiocyanate is widely present in cruciferous vegetables with multiple biological effects. Here we reported the antiatherogenic effects and the underlying mechanisms of JC-5411 (Phenethyl isothiocyanate formulation) in vitro and in vivo. Luciferase reporter assay showed that JC-5411 increased the activity ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.532568
更新日期:2020-11-16 00:00:00
abstract::Objective: To evaluate therapeutic efficacy of different combined antimicrobial treatments against Acinetobacter baumannii ventilator-associated pneumonia (VAP). Methods: Clinical outcomes were retrospectively analyzed to elucidate the efficacy of four combined antimicrobial regimens. The chessboard and micro broth di...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.00092
更新日期:2019-02-13 00:00:00
abstract::The lignan-rich fraction (SWR) of Sambucus Williamsii Ramulus, a folk herbal medicine in China for treatment of bone diseases, has previously reported to exert protective effects on bone without exerting uterotrophic effects in ovariectomized (OVX) mice. The aim of the present study was to identify the potential metab...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00932
更新日期:2018-08-21 00:00:00
abstract::Background: Modeling and simulation is increasingly used to study pediatric pharmacokinetics, but clinical implementation of age-appropriate doses lags behind. Therefore, we aimed to develop model-informed doses using published pharmacokinetic data and a decision framework to adjust dosing guidelines based on these do...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.592204
更新日期:2020-12-16 00:00:00
abstract::Lapatinib, targeting the human epidermal growth factor receptor family members HER1 and HER2, has been approved by the US Food and Drug Administration for use in metastatic HER2-positive breast cancer. However, resistance to lapatinib remains a common challenge to HER2-positive metastatic breast cancer. Until now, the...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.577150
更新日期:2020-09-04 00:00:00
abstract::Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase recently implicated in biochemical, physiological, and behavioral responses to ethanol. Thus, manipulation of ALK signaling may represent a novel approach to treating alcohol use disorder (AUD). Ethanol induces adaptations in glutamatergic synapses onto nu...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00533
更新日期:2017-08-15 00:00:00
abstract::Background: D-dimer is a small protein fragment and high levels of D-dimer have been associated with increased mortality in patients presenting to emergency departments with infection. Previous studies have reported increased levels of D-dimer in COVID-19; however, it is unclear whether an increased D-dimer level prov...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.600592
更新日期:2020-12-21 00:00:00
abstract::There is growing evidence that the metabolic network is an integral regulator of cellular physiology. Dynamic changes in metabolite concentrations, metabolic flux, or network topology act as reporters of biological or environmental signals, and are required for the cell to trigger an appropriate biological reaction. C...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2012.00032
更新日期:2012-03-08 00:00:00
abstract::The ATP-gated P2X7 ion channel is an abundant microglial protein in the CNS that plays an important pathological role in executing ATP-driven danger signal transduction. Emerging data has generated scientific interest and excitement around targeting the P2X7 ion channel as a potential drug target for CNS disorders. Ov...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2018.00030
更新日期:2018-02-01 00:00:00
abstract:Background:Patients with locally advanced rectal cancer (LARC) are at higher risk of local and distant recurrence and are thus more vulnerable to metastatic diseases. Neoadjuvant chemoradiotherapy (nCRT) and subsequent curative resection with total mesorectal excision (TME) followed by adjuvant chemotherapy have been r...
journal_title:Frontiers in pharmacology
pub_type:
doi:10.3389/fphar.2020.00706
更新日期:2020-05-15 00:00:00
abstract::PIN1 is a member of a family of peptidylprolyl isomerases that bind phosphoproteins and catalyze the rapid cis-trans isomerization of proline peptidyl bonds, resulting in an alteration of protein structure, function, and stability. PIN1 is overexpressed in human cancers, suggesting it promotes tumorigenesis, but depen...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.01477
更新日期:2019-01-22 00:00:00
abstract::Background: Up to date, the efficacy and safety of warfarin treatment in atrial fibrillation patients receiving hemodialysis remain controversial. So we performed this meta-analysis to try to offer recommendations regarding warfarin management in this population. Methods: We searched Pubmed, Embase, and Cochrane libra...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.01218
更新日期:2018-11-06 00:00:00
abstract::Endocrine fibroblast growth factor (FGF) 19 has been shown to be capable of maintaining bile acid (BA) homeostasis and thus hold promise to be a potential therapeutic agent for cholestasis liver disease. However, whether paracrine FGFs possess this BA regulatory activity remains to be determined. In our study, we iden...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.01515
更新日期:2019-12-20 00:00:00
abstract::Acute lung injury (ALI) is a complex syndrome with sepsis occurring in critical patients, who usually lack effective therapy. Nuciferine is a primary bioactive component extracted from the lotus leaf, and it displays extensive pharmacological functions, including anti-cancer, anti-inflammatory, and antioxidant propert...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00939
更新日期:2017-12-21 00:00:00
abstract::Chronic pain is a common detrimental condition that affects around 20% of the world population. The current drugs to treat chronic pain states, especially neuropathic pain, have a limited clinical efficiency and present significant adverse effects that complicates their regular use. Recent studies have proposed new th...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2020.00167
更新日期:2020-03-03 00:00:00
abstract::Metabotropic glutamate (mGlu) receptor 5 is involved in neuroinflammation and has been shown to mediate reduced inflammation and neurotoxicity and to modify microglia polarization. On the other hand, blockade of mGlu5 receptor results in inhibition of microglia activation. To dissect this controversy, we investigated ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00812
更新日期:2017-11-09 00:00:00
abstract::Drug-induced liver injury (DILI) is a major clinical problem where natural compounds hold promise for its abrogation. Khaya grandifoliola (Meliaceae) is used in Cameroonian traditional medicine for the treatment of liver related diseases and has been studied for its hepatoprotective properties. Till date, reports show...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00653
更新日期:2017-09-19 00:00:00
abstract::P-Glycoprotein (P-gp, Abcb1) plays a crucial role in drug disposition and functions by hydrolyzing ATP. However, little is known about the regulatory elements governing the transcription of the porcine Abcb1 gene. In this study, the transcription start site of the pig Abcb1 gene was identified by 5'-RACE. A 1.9-kb fra...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00373
更新日期:2018-05-04 00:00:00
abstract::Stability of traditional Chinese medicine injection (TCMI) is an important issue related with its clinical application. TCMI is composed of multi-components, therefore, when evaluating TCMI stability, several marker compounds cannot represent global components or biological activities of TCMI. Till now, when evaluatin...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00833
更新日期:2017-11-15 00:00:00
abstract:Objective:Current prevention and/or treatment options for respiratory syncytial virus (RSV) infections are limited as no vaccine is available. Prophylaxis with palivizumab is very expensive and requires multiple intramuscular injections over the RSV season. Here we present proof-of-concept data using nebulized palivizu...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.01291
更新日期:2020-08-19 00:00:00
abstract::The Health Improvement Network UK primary care database was used to identify a cohort of 38 077 individuals aged 50-84 years with a first prescription of low-dose acetylsalicylic acid (ASA; 75-300 mg/day) for secondary prevention of cardiovascular or cerebrovascular events during 2000-2007. From this cohort, 169 incid...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2010.00126
更新日期:2010-10-14 00:00:00