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Marcelo R Luizon, Daniela A Pereira, Valeria C Sandrim
Hypertension is a leading cause of cardiovascular mortality, but only about half of patients on antihypertensive therapy achieve blood pressure control. Preeclampsia is defined as pregnancy-induced hypertension and proteinuria, and is associated with increased maternal and perinatal mortality and morbidity. Similarly, a large number of patients with preeclampsia are non-responsive to antihypertensive therapy. Pharmacogenomics may help to guide the personalized treatment for non-responsive hypertensive patients...
2018: Frontiers in Pharmacology
Francesca Maria Notarangelo, Giuseppe Maglietta, Paola Bevilacqua, Marco Cereda, Piera Angelica Merlini, Giovanni Quinto Villani, Paolo Moruzzi, Giampiero Patrizi, Guidantonio Malagoli Tagliazucchi, Antonio Crocamo, Angela Guidorossi, Filippo Pigazzani, Elisa Nicosia, Giorgia Paoli, Marco Bianchessi, Mario Angelo Comelli, Caterina Caminiti, Diego Ardissino
BACKGROUND: Clopidogrel is still frequently used in patients with acute coronary syndromes (ACS), but its efficacy is hampered by interpatient response variability, due to genetic polymorphisms associated with clopidogrel metabolism. OBJECTIVE: To evaluate whether selecting antiplatelet therapy (clopidogrel, prasugrel or ticagrelor) on the basis of a patient's genetic and clinical characteristics leads to better clinical outcomes in comparison with the standard of care, which bases the selection on clinical characteristics alone METHODS: Patients hospitalised for ACS were randomly assigned to standard of care or pharmacogenomic arm, which included the genotyping of ABCB1, CYP2C19*2, CYP2C19*17 using an ST Q3 system that provide the data within 70 minutes at each patient's bedside...
February 24, 2018: Journal of the American College of Cardiology
Mario Cazzola, Luigino Calzetta, Maria Gabriella Matera, Nicola A Hanania, Paola Rogliani
Our understanding of whether and/or how ethnicity influences pharmacological response to asthma therapies is still very scarce. A possible explanation for the increased asthma treatment failures observed in ethnic and racial minorities receiving asthma therapies is that some of these groups may have a pharmacogenomic predisposition to either nonresponse or to adverse response with a specific class of drugs. However, the effects of ethnicity on pharmacological response to asthma therapies are also, and mainly, determined by socioeconomic and environmental factors to a varying extent, depending on the ethnic groups...
March 12, 2018: Expert Opinion on Drug Metabolism & Toxicology
Youqiong Ye, Yu Xiang, Fatma Muge Ozguc, Yoonjin Kim, Chun-Jie Liu, Peter K Park, Qingsong Hu, Lixia Diao, Yanyan Lou, Chunru Lin, An-Yuan Guo, Bingying Zhou, Li Wang, Zheng Chen, Joseph S Takahashi, Gordon B Mills, Seung-Hee Yoo, Leng Han
Cancer chronotherapy, treatment at specific times during circadian rhythms, endeavors to optimize anti-tumor effects and to lower toxicity. However, comprehensive characterization of clock genes and their clinical relevance in cancer is lacking. We systematically characterized the alterations of clock genes across 32 cancer types by analyzing data from The Cancer Genome Atlas, Cancer Therapeutics Response Portal, and The Genomics of Drug Sensitivity in Cancer databases. Expression alterations of clock genes are associated with key oncogenic pathways, patient survival, tumor stage, and subtype in multiple cancer types...
March 1, 2018: Cell Systems
Sonal Singh, Caitrin W McDonough, Yan Gong, Wael A Alghamdi, Meghan J Arwood, Salma A Bargal, Leanne Dumeny, Wen-Yi Li, Mai Mehanna, Bradley Stockard, Guang Yang, Felipe A de Oliveira, Natalie C Fredette, Mohamed H Shahin, Kent R Bailey, Amber L Beitelshees, Eric Boerwinkle, Arlene B Chapman, John G Gums, Stephen T Turner, Rhonda M Cooper-DeHoff, Julie A Johnson
BACKGROUND: Thiazide and thiazide-like diuretics are first-line medications for treating uncomplicated hypertension. However, their use has been associated with adverse metabolic events, including hyperglycemia and incident diabetes mellitus, with incompletely understood mechanisms. Our goal was to identify genomic variants associated with thiazide-like diuretic/chlorthalidone-induced glucose change. METHODS AND RESULTS: Genome-wide analysis of glucose change after treatment with chlorthalidone was performed by race among the white (n=175) and black (n=135) participants from the PEAR-2 (Pharmacogenomic Evaluation of Antihypertensive Responses-2)...
March 9, 2018: Journal of the American Heart Association
Prema S Rao, Ryan Endicott, Randy Mullins, U Subrahmanyeswara Rao
Comparison of human genome sequences from different individuals has unraveled that genes involved in the drug efficacy and metabolism are polymorphic, harboring mutations, splicing variations and other alterations. These data provide a reasonable explanation for the inter-individual variations observed in drug therapy. Thus, a detailed molecular analysis and an in-depth knowledge of these genes is a prerequisite to practice pharmacogenomics-based medicine. We have introduced a 6-week laboratory research rotation to train students in the expression analysis of different pharmacogenes combined with bioinformatics tools...
March 8, 2018: Pharmacogenomics Journal
Shyan Goh
No abstract text is available yet for this article.
February 2018: Australian Prescriber
Hao Yu, Hao Yan, Lifang Wang, Jun Li, Liwen Tan, Wei Deng, Qi Chen, Guigang Yang, Fuquan Zhang, Tianlan Lu, Jianli Yang, Keqing Li, Luxian Lv, Qingrong Tan, Hongyan Zhang, Xiao Xiao, Ming Li, Xin Ma, Fude Yang, Lingjiang Li, Chuanyue Wang, Tao Li, Dai Zhang, Weihua Yue
BACKGROUND: Antipsychotic drugs improve schizophrenia symptoms and reduce the frequency of relapse, but treatment response is highly variable. Little is known about the genetic factors associated with treatment response. We did a genome-wide association study of antipsychotic treatment response in patients with schizophrenia. METHODS: The discovery cohort comprised patients with schizophrenia from 32 psychiatric hospitals in China that are part of the Chinese Antipsychotics Pharmacogenomics Consortium...
March 1, 2018: Lancet Psychiatry
Kathryn T Hall, Joseph Loscalzo, Ted Kaptchuk
There is perhaps no more important time in the history of placebos to consider their role in clinical trials and in medicine. Increasingly well-designed pharmaceutical and academic clinical trials testing promising and established drug and surgical interventions have failed to "beat" the placebo response. The collateral damage resulting from these failures is staggering; novel treatments, many with compelling mechanisms of action and promising Phase 2 trial results, never reach the patient, adversely affecting small and large pharma alike...
March 2, 2018: ACS Chemical Neuroscience
Srini Chary
Methadone for pain management in this article describes briefly pain, methadone as a Level 3 World Health Organization ladder opioid in the context of India and rest of the world, as well as the relationship to past, present, and future possibilities of pain management. Acute pain is proportional to the injury most of the times, and such proportionality may not exist in chronic pain. Pain management over decades has changed because of knowledge and availability of molecules and compounds to reduce chronic pain...
January 2018: Indian Journal of Palliative Care
Ayman F El-Kattan, Manthena V S Varma
Membrane transporters play an important role in the absorption, distribution, clearance and elimination (ADCE) of the drugs. Supported by the pharmacokinetics data in human, several transporters including organic anion transporting polypeptide (OATP)1B1, OATP1B3, organic anion transporter (OAT)1, OAT3, organic cation transporter (OCT)2, multidrug and toxin extrusion proteins (MATEs), P-glycoprotein and breast cancer resistance protein (BCRP) are suggested to be of clinical relevance. An early understanding of transporters role in the drug disposition and clearance allows reliable prediction/evaluation of the pharmacokinetic changes due to drug-drug interactions (DDIs) or genetic polymorphisms...
March 1, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Kenneth Wysocki
Research and application of genomic medicine in lung disease during the past century has clarified our understanding and focus on specific phenotypes, helping clinicians tailor treatment for individual patients. Cystic fibrosis and lung cancer have been researched extensively; specific genotypes have been instrumental in precision medicine to treat these lung diseases. Asthma and chronic obstructive pulmonary disease are more complex and heterogeneous in their pathogenesis, genotypic profile, and phenotypic expression, making treatment more difficult with increasing disease severity...
2018: AACN Advanced Critical Care
Dennis Cheek, Lynnette Howington
Since the successful completion of the Human Genome Project in 2003, extensive genomic research has continued to alter pathophysiology at the molecular level. This research includes investigation of the specific receptors and metabolizing enzymes in drug pharmacodynamics and pharmacokinetics, specifically the cytochrome P450 system located primarily in the liver. In this article, pharmacogenomics and the role of the cytochrome P450 system in metabolism of various drugs are discussed. Specifically, drugs that are used in the critical care setting and are of clinical significance to the bedside critical care nurse are examined...
2018: AACN Advanced Critical Care
Niloufar Farzan, Susanne J Vijverberg, Michael Kabesch, Peter J Sterk, Anke H Maitland-van der Zee
Asthma is a complex multifactorial disease and it is the most common chronic disease in children. There is a high variability in response to asthma treatment, even in patients with good adherence to maintenance treatment, and a correct inhalation technique. Distinct underlying disease mechanisms in childhood asthma might be the reason of this heterogeneity. A deeper knowledge of the underlying molecular mechanisms of asthma has led to the recent development of advanced and mechanism-based treatments such as biologicals...
March 1, 2018: Pediatric Pulmonology
Juan Xie, Anjun Ma, Anne Fennell, Qin Ma, Jing Zhao
Biclustering is a powerful data mining technique that allows clustering of rows and columns, simultaneously, in a matrix-format data set. It was first applied to gene expression data in 2000, aiming to identify co-expressed genes under a subset of all the conditions/samples. During the past 17 years, tens of biclustering algorithms and tools have been developed to enhance the ability to make sense out of large data sets generated in the wake of high-throughput omics technologies. These algorithms and tools have been applied to a wide variety of data types, including but not limited to, genomes, transcriptomes, exomes, epigenomes, phenomes and pharmacogenomes...
February 27, 2018: Briefings in Bioinformatics
Ferdous A Jabir, Wisam H Hoidy
BACKGROUND: Breast cancer is the most common cancer in women characterized by a high variable clinical outcome among individuals treated with targeted therapies. PATIENTS AND METHODS: In this study, we performed a population-based approach intersecting high-throughput genotype data from Iraqi populations with publicly available pharmacogenomics information to estimate the frequency of genotypes correlated with responsiveness to breast cancer treatment thus improving the clinical management of this disease in an efficient and cost effective way...
January 31, 2018: Clinical Breast Cancer
Mohamed H Shahin, Daniela J Conrado, Daniel Gonzalez, Yan Gong, Maximilian T Lobmeyer, Amber L Beitelshees, Eric Boerwinkle, John G Gums, Arlene Chapman, Stephen T Turner, Rhonda M Cooper-DeHoff, Julie A Johnson
BACKGROUND: For many indications, the negative chronotropic effect of β-blockers is important to their efficacy, yet the heart rate (HR) response to β-blockers varies. Herein, we sought to use a genome-wide association approach to identify novel single nucleotide polymorphisms (SNPs) associated with HR response to β-blockers. METHODS AND RESULTS: We first performed 4 genome-wide association analyses for HR response to atenolol (a β1-adrenergic receptor blocker) as: (1) monotherapy or (2) add-on therapy, in 426 whites and 273 blacks separately from the PEAR (Pharmacogenomic Evaluation of Antihypertensive Responses) study...
February 24, 2018: Journal of the American Heart Association
John M Pascoe
No abstract text is available yet for this article.
February 2018: Current Problems in Pediatric and Adolescent Health Care
Karthikeyan Muthusamy, Selvaraman Nagamani
Pharmacogenetics and pharmacogenomics have become presumptive with advancements in next-generation sequencing technology. In complex diseases, distinguishing the feasibility of pathogenic and neutral disease-causing variants is a time consuming and expensive process. Recent drug research and development processes mainly rely on the relationship between the genotype and phenotype through Single nucleotide polymorphisms (SNPs). The SNPs play an indispensable role in elucidating the individual's vulnerability to disease and drug response...
February 12, 2018: Journal of Molecular Graphics & Modelling
Julia M Barbarino, Michelle Whirl-Carrillo, Russ B Altman, Teri E Klein
As precision medicine becomes increasingly relevant in healthcare, the field of pharmacogenomics (PGx) also continues to gain prominence in the clinical setting. Leading institutions have begun to implement PGx testing and the amount of published PGx literature increases yearly. The Pharmacogenomics Knowledgebase (PharmGKB; is one of the foremost worldwide resources for PGx knowledge, and the organization has been adapting and refocusing its mission along with the current revolution in genomic medicine...
February 23, 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
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