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pharmacogenomics

These pubmed results were generated on 2019/10/09

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.

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 2019/10/08

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.

Southeast Asian Pharmacogenomics Research Network (SEAPharm): Current Status and Perspectives.

Public Health Genomics. 2019 Oct 04;:1-8

Authors: Chumnumwat S, Lu ZH, Sukasem C, Winther MD, Capule FR, Abdul Hamid AAAT, Bhandari B, Chaikledkaew U, Chanhom N, Chantarangsu S, Charoenyingwattana A, Hang TT, Hlaing TM, Htun KS, Jittikoon J, Le L, Mahasirimongkol S, Mohamed Noor DA, Shrestha J, Suwannoi L, Tragulpiankit P, Turongkaravee S, Wattanapokayakit S, Xangsayarath P, Yuliwulandari R, Zain SM, Chantratita W

Abstract
Pharmacogenomics (PGx) is increasingly being recognized as a potential tool for improving the efficacy and safety of drug therapy. Therefore, several efforts have been undertaken globally to facilitate the implementation process of PGx into routine clinical practice. Part of these efforts include the formation of PGx working groups working on PGx research, synthesis, and dissemination of PGx data and creation of PGx implementation strategies. In Asia, the Southeast Asian Pharmacogenomics Research Network (SEAPharm) is established to enable and strengthen PGx research among the various PGx communities within but not limited to countries in SEA; with the ultimate goal to support PGx implementation in the region. From the perspective of SEAPharm member countries, there are several key elements essential for PGx implementation at the national level. They include pharmacovigilance database, PGx research, health economics research, dedicated laboratory to support PGx testing for both research and clinical use, structured PGx education, and supportive national health policy. The status of these essential elements is presented here to provide a broad picture of the readiness for PGx implementation among the SEAPharm member countries, and to strengthen the PGx research network and practice in this region.

PMID: 31587001 [PubMed - as supplied by publisher]

The impact of steroids on the injured podocytes in nephrotic syndrome.

J Steroid Biochem Mol Biol. 2019 Oct 03;:105490

Authors: Hosseiniyan Khatibi SM, Ardalan M, Abediazar S, Vahed SZ

Abstract
Nephrotic syndrome (NS), a common chronic kidney disease, embraces a variety of kidney disorders. Though Glucocorticoids (GCs) are generally used in the treatment of NS, their mechanism of action is poorly understood. A plethora of evidence indicates that podocytes are considered as the main target cells for the therapeutic strategies to prevent NS. GCs regulate the transactivation and transrepression of genes in podocytes that affect their morphological and cytoskeletal features, motility, apoptosis, and survival rate. Moreover, they prevent protein leakage through the glomerular barrier membrane by affecting the synthesis, trafficking, and posttranslational modifications of slit diaphragms components, podocytes' intercellular junctions. The response to the treatment is variable among different ethnics and populations and resistance to the steroids is detected in almost 50% of adult patients. Not only do pharmacokinetics and pharmacogenetics of steroids play a role in GC resistance but also the genetic variations in one or more podocyte related genes are connected with the steroid resistance in cases with NS. The focus of this review is to explain the underlying cellular and molecular mechanisms of GCs in podocytes. Understanding the mechanisms by which the GCs and GCs receptors in podocytes regulate the gene expression network and crosstalk with other molecular pathways would guarantee an optimum therapeutic benefit of steroid treatment.

PMID: 31586640 [PubMed - as supplied by publisher]

Comparison of effects of UGT1A1*6 and UGT1A1*28 on irinotecan-induced adverse reactions in the Japanese population: analysis of the Biobank Japan Project.

J Hum Genet. 2019 Oct 04;:

Authors: Hikino K, Ozeki T, Koido M, Terao C, Kamatani Y, Murakami Y, Kubo M, Mushiroda T

Abstract
It has been reported that there are differences in effects on irinotecan-induced adverse reactions between UGT1A1*6 and UGT1A1*28. In order to compare those differences in the Japanese population, we examined the associations between UGT1A1 and irinotecan-induced adverse reactions using the BioBank Japan Project database. We genotyped UTG1A1*6 and UGT1A1*28 and conducted case-control analyses. A total of 651 patients (102 cases and 549 tolerant controls) were included in this study. The results showed that UGT1A1*6/*6 is a predictor of adverse drug reactions (ADRs) (p-value 0.00070, odds ratio 6.59, 95% confidence interval 2.33-18.6), whereas UGT1A1*6/*28 and UGT1A1*28/*28 were not. The subanalysis comprising only patients with UGT1A1*6/*6, UGT1A1*6/*28, and UGT1A1*28/*28 revealed a trend towards an increased risk of ADRs in patients with UGT1A1*6 (p-value 0.0092, odds ratio 4.39, 95% confidence interval 1.57-14.9). Multiple logistic regression analyses showed that use of platinum-based antineoplastic drugs and presence of UGT1A1*6/*6 were independent variables, significantly associated with ADRs. The diagnostic performance of a predictive model had a sensitivity of 49.0%, specificity of 70.1%, and a number needed to screen of 5.8. We concluded that UGT1A1 testing could be useful to predict irinotecan-induced ADRs, and that UTG1A1*6 rather than UGT1A1*28 contributed to ADR occurrence.

PMID: 31586129 [PubMed - as supplied by publisher]

The Future of Precision Medicine.

Clin Pharmacol Ther. 2019 Nov;106(5):903-906

Authors: Verstegen RHJ, Ito S

Abstract
Precision medicine is an emerging framework to maximize therapeutic benefit by modifying the treatment for individual patients based on their variations in demographic, genomic, and environmental factors. In particular, "Pharmacogenomics" and "Therapeutic Drug Monitoring" are key elements of individualized drug treatment, staging Clinical Pharmacology at the forefront of precision medicine.

PMID: 31584718 [PubMed - in process]

Is Pharmacogenetics Useful in Antidepressant Treatment?

Clin Pharmacol Ther. 2019 Nov;106(5):916-918

Authors: Fabbri C, Serretti A

PMID: 31584716 [PubMed - in process]

Development of an Inexpensive and Rapid Operation Device for High-Throughput Real-Time Quantitative PCR-Based CYP2D6 CNV Genotyping.

Biol Pharm Bull. 2019;42(10):1761-1765

Authors: Imai M, Kisoi M, Moritsugu M, Murata S, Ichikawa A, Kinoshita K

Abstract
The CYP2D6 gene is the most well characterized gene involved in drug metabolism and is known to have both gene duplication and deletion variants. We report an optimized method for the determination of copy number variation (CNV) in the CYP2D6 gene by a novel purification process for a real-time quantitative PCR. This high-throughput low-cost method accurately determines CNV in the CYP2D6 gene enabling reliable estimates of disease prediction in large epidemiological samples.

PMID: 31582664 [PubMed - in process]

[Development of Stratified and Personalized Medicine Based on Pharmacogenomic and Pharmacokinetic Analyses].

Yakugaku Zasshi. 2019;139(10):1253-1258

Authors: Hirai K

Abstract
To administer optimal and safe pharmacotherapy, development of stratified and personalized therapy is imperative. Pharmacogenomics (PGx) is useful in elucidating factors causing individual differences in drug efficacy and the emergence of adverse effects. It also helps design accurate drug administration methods by evaluating the effects of patient-related factors, such as genetic factors, that influence pharmacokinetics (PK) and pharmacodynamics (PD). In addition, selection of appropriate therapeutic agents requires the implementation of precision medicine allowing accurate disease diagnosis. To establish precision medicine, it is necessary to uncover the association of pathophysiological factors, which are represented as endotype or genotype, with the pathology of several phenotypes. This review describes two aspects related to realization of individualized medicine, namely the effectiveness of PK/PD/PGx studies and the stratification of pathological conditions. First, we conducted a PK/PD/PGx study with the aim to individualize warfarin treatment. In this study, we elucidated the effect of CYP4F2 polymorphisms associated with vitamin K metabolism by measuring the blood concentrations of warfarin and vitamin K. Then, to develop precision medicine for asthma and chronic obstructive pulmonary disease (COPD), we analyzed not only clinical symptoms but also pathological biomarkers and genes associated with inflammation. The findings may contribute toward better understanding of the pathological conditions of asthma, COPD, and asthma-COPD overlap.

PMID: 31582608 [PubMed - in process]

Pharmacogenomics: Prescribing Precisely.

Med Clin North Am. 2019 Nov;103(6):977-990

Authors: Wake DT, Ilbawi N, Dunnenberger HM, Hulick PJ

Abstract
Pharmacogenomics (PGx) is a powerful tool that can predict increased risks of adverse effects and sub-therapeutic response to medications. This article establishes the core principles necessary for a primary care provider to meaningfully and prudently use PGx testing. Key topics include in which patients PGx testing should be considered, how PGx tests are ordered, how the results are translated into clinical recommendations, and what further advancements are likely in the near future. This will provide clinicians with a foundational knowledge of PGx that can allow incorporation of this tool into their practice or support further personal investigation.

PMID: 31582008 [PubMed - in process]

Examining the role of precision medicine with oral baclofen in pediatric patients with cerebral palsy.

Curr Phys Med Rehabil Rep. 2019 Mar;7(1):40-45

Authors: McLaughlin MJ, Abdel-Rahman S, Leeder JS

Abstract
Purpose of review: a)Despite its widespread use, oral baclofen requires a critical review of the pharmacology to determine potential precision medicine applications to improve medication administration. Discussing the dose→exposure→response relationship of oral baclofen allows a conceptual framework in which designing clinical trials would become more successful. This paper seeks to examine some of the areas where variability in exposures can exist lead to undesired clinical responses.
Recent findings: b)Several factors are at play to implement precision medicine with oral baclofen in the pediatric patient with cerebral palsy. Variations in intestinal absorption, oral baclofen clearance, pharmacogenomic variants, and distribution of this medication into the cerebrospinal fluid cause differences in the amount of baclofen available at the GABA-B receptor site to cause a clinical response.
Summary: c)Oral baclofen has significant variability in disposition and clinical response. Research to determine the causes for this variability and controlling for these factors would allow improvement in clinical outcomes.

PMID: 31579558 [PubMed]

A Quarter Century of PCR-Applied Techniques and Their Still-Increasing Fields of Use.

Methods Mol Biol. 2020;2065:1-4

Authors: Raso A, Biassoni R

Abstract
Quantitative polymerase chain reaction (PCR) is the basis of a variety of scientific applications and publications in a broad range of interests. It also plays a fundamental role in nucleic acid sequencing applications, including Next Generation Sequencing (NGS)-based ones. The potential of PCR diagnostics is enormous, particularly for the early diagnosis of life-threatening infections. Some other fields of applications that use PCR on a regular basis include oncology, genetics, microbiology, biochemistry, immunogenetics, NGS, ecology, comparative genome evolution, ancestry DNA, pharmacogenomics, personalized medicine, and even general medicine.

PMID: 31578683 [PubMed - in process]

DTC pharmacogenomics testing under scrutiny.

Nat Biotechnol. 2019 Oct;37(10):1101

Authors:

PMID: 31578506 [PubMed - in process]

Towards precision medicine: interrogating the human genome to identify drug pathways associated with potentially functional, population-differentiated polymorphisms.

Pharmacogenomics J. 2019 Oct 03;:

Authors: Bachtiar M, Ooi BNS, Wang J, Jin Y, Tan TW, Chong SS, Lee CGL

Abstract
Drug response variations amongst different individuals/populations are influenced by several factors including allele frequency differences of single nucleotide polymorphisms (SNPs) that functionally affect drug-response genes. Here, we aim to identify drugs that potentially exhibit population differences in response using SNP data mining and analytics. Ninety-one pairwise-comparisons of >22,000,000 SNPs from the 1000 Genomes Project, across 14 different populations, were performed to identify 'population-differentiated' SNPs (pdSNPs). Potentially-functional pdSNPs (pf-pdSNPs) were then selected, mapped into genes, and integrated with drug-gene databases to identify 'population-differentiated' drugs enriched with genes carrying pf-pdSNPs. 1191 clinically-approved drugs were found to be significantly enriched (Z > 2.58) with genes carrying SNPs that were differentiated in one or more population-pair comparisons. Thirteen drugs were found to be enriched with such differentiated genes across all 91 population-pairs. Notably, 82% of drugs, which were previously reported in the literature to exhibit population differences in response were also found by this method to contain a significant enrichment of population specific differentiated SNPs. Furthermore, drugs with genetic testing labels, or those suspected to cause adverse reactions, contained a significantly larger number (P < 0.01) of population-pairs with enriched pf-pdSNPs compared with those without these labels. This pioneering effort at harnessing big-data pharmacogenomics to identify 'population differentiated' drugs could help to facilitate data-driven decision-making for a more personalized medicine.

PMID: 31578463 [PubMed - as supplied by publisher]

A pediatric perspective on genomics and prevention in the twenty-first century.

Pediatr Res. 2019 Oct 02;:

Authors: Chaudhari BP, Manickam K, McBride KL

Abstract
We present evidence from diverse disciplines and populations to identify the current and emerging role of genomics in prevention from both medical and public health perspectives as well as key challenges and potential untoward consequences of increasing the role of genomics in these endeavors. We begin by comparing screening in healthy populations (newborn screening), with testing in symptomatic populations, which may incidentally identify secondary findings and at-risk relatives. Emerging evidence suggests that variants in genes subject to the reporting of secondary findings are more common than expected in patients who otherwise would not meet the criteria for testing and population testing for variants in these genes may more precisely identify discrete populations to target for various prevention strategies starting in childhood. Conversely, despite its theoretical promise, recent studies attempting to demonstrate benefits of next-generation sequencing for newborn screening have instead demonstrated numerous barriers and pitfalls to this approach. We also examine the special cases of pharmacogenomics and polygenic risk scores as examples of ways genomics can contribute to prevention amongst a broader population than that affected by rare Mendelian disease. We conclude with unresolved questions which will benefit from future investigations of the role of genomics in disease prevention.

PMID: 31578042 [PubMed - as supplied by publisher]

Genetics and pharmacogenetics in the diagnosis and therapy of cardiovascular diseases.

Acta Biomed. 2019 Sep 30;90(10-S):7-19

Authors: Krasi G, Precone V, Paolacci S, Stuppia L, Nodari S, Romeo F, Perrone M, Bushati V, Dautaj A, Bertelli M

Abstract
Cardiovascular diseases are the main cause of death worldwide. The ability to accurately define individual susceptibility to these disorders is therefore of strategic importance. Linkage analysis and genome-wide association studies have been useful for the identification of genes related to cardiovascular diseases. The identification of variants predisposing to cardiovascular diseases contributes to the risk profile and the possibility of tailored preventive or therapeutic strategies. Molecular genetics and pharmacogenetics are playing an increasingly important role in the correct clinical management of patients. For instance, genetic testing can identify variants that influence how patients metabolize medications, making it possible to prescribe personalized, safer and more efficient treatments, reducing medical costs and improving clinical outcomes. In the near future we can expect a great increment in information and genetic testing, which should be acknowledged as a true branch of diagnostics in cardiology, like hemodynamics and electrophysiology. In this review we summarize the genetics and pharmacogenetics of the main cardiovascular diseases, showing the role played by genetic information in the identification of cardiovascular risk factors and in the diagnosis and therapy of these conditions.

PMID: 31577248 [PubMed - in process]

Antidiabetic Potential of Medicinal Plants and Their Active Components.

Biomolecules. 2019 Sep 30;9(10):

Authors: Salehi B, Ata A, V Anil Kumar N, Sharopov F, Ramírez-Alarcón K, Ruiz-Ortega A, Abdulmajid Ayatollahi S, Tsouh Fokou PV, Kobarfard F, Amiruddin Zakaria Z, Iriti M, Taheri Y, Martorell M, Sureda A, Setzer WN, Durazzo A, Lucarini M, Santini A, Capasso R, Ostrander EA, Atta-ur-Rahman, Choudhary MI, Cho WC, Sharifi-Rad J

Abstract
Diabetes mellitus is one of the major health problems in the world, the incidence and associated mortality are increasing. Inadequate regulation of the blood sugar imposes serious consequences for health. Conventional antidiabetic drugs are effective, however, also with unavoidable side effects. On the other hand, medicinal plants may act as an alternative source of antidiabetic agents. Examples of medicinal plants with antidiabetic potential are described, with focuses on preclinical and clinical studies. The beneficial potential of each plant matrix is given by the combined and concerted action of their profile of biologically active compounds.

PMID: 31575072 [PubMed - in process]

A Humanized Yeast Phenomic Model of Deoxycytidine Kinase to Predict Genetic Buffering of Nucleoside Analog Cytotoxicity.

Genes (Basel). 2019 Sep 30;10(10):

Authors: Santos SM, Icyuz M, Pound I, William D, Guo J, McKinney BA, Niederweis M, Rodgers J, Iv JLH

Abstract
Knowledge about synthetic lethality can be applied to enhance the efficacy of anticancer therapies in individual patients harboring genetic alterations in their cancer that specifically render it vulnerable. We investigated the potential for high-resolution phenomic analysis in yeast to predict such genetic vulnerabilities by systematic, comprehensive, and quantitative assessment of drug-gene interaction for gemcitabine and cytarabine, substrates of deoxycytidine kinase that have similar molecular structures yet distinct antitumor efficacy. Human deoxycytidine kinase (dCK) was conditionally expressed in the Saccharomyces cerevisiae genomic library of knockout and knockdown (YKO/KD) strains, to globally and quantitatively characterize differential drug-gene interaction for gemcitabine and cytarabine. Pathway enrichment analysis revealed that autophagy, histone modification, chromatin remodeling, and apoptosis-related processes influence gemcitabine specifically, while drug-gene interaction specific to cytarabine was less enriched in gene ontology. Processes having influence over both drugs were DNA repair and integrity checkpoints and vesicle transport and fusion. Non-gene ontology (GO)-enriched genes were also informative. Yeast phenomic and cancer cell line pharmacogenomics data were integrated to identify yeast-human homologs with correlated differential gene expression and drug efficacy, thus providing a unique resource to predict whether differential gene expression observed in cancer genetic profiles are causal in tumor-specific responses to cytotoxic agents.

PMID: 31575041 [PubMed - in process]

The Influences of Adherence to Tamoxifen and CYP2D6 Pharmacogenetics on Plasma Concentrations of the Active Metabolite (Z)-Endoxifen in Breast Cancer.

Clin Transl Sci. 2019 Oct 01;:

Authors: Nardin JM, Schroth W, Almeida TA, Mürdter T, Picolotto S, Vendramini ECL, Hoppe R, Kogin JP, Miqueleto D, de Moraes SDR, Schwab M, Pecoits-Filho RF, Brauch H, Casali-da-Rocha JC

Abstract
Tamoxifen efficacy in breast cancer is suspected to depend on adherence and intact drug metabolism. We evaluated the role of adherence behavior and pharmacogenetics on the formation rate of (Z)-endoxifen. In 192 Brazilian patients we assessed plasma levels of tamoxifen and its metabolites at 3, 6, and 12 months of treatment (LC-MS/MS), adherence behavior (Morisky medication adherence scale), and CYP2D6 and other pharmacogene polymorphisms (MALDI-TOF mass spectrometry, real-time PCR). Adherence explained 47% of the variability of tamoxifen plasma concentrations (P<.001). While CYP2D6 alone explained 26.4%, the combination with adherence explained 40% of (Z)-endoxifen variability at 12 months (P<.001). The influence of low adherence to not achieving relevant (Z)-endoxifen levels was highest in patients with non-compromised CYP2D6 function (RR 3.65, 95% CI: 1.48-8.99). As a proof-of-concept we demonstrated that (Z)-endoxifen levels are influenced both by patient adherence to tamoxifen and CYP2D6 which is particularly relevant for patients with full CYP2D6 function.

PMID: 31573754 [PubMed - as supplied by publisher]

Editorial: Establishing Genetic Pleiotropy to Identify Common Pharmacological Agents for Common Diseases.

Front Pharmacol. 2019;10:1038

Authors: O'Mara TA, Batra J, Glubb D

PMID: 31572202 [PubMed]