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Pharmacogenetic

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https://www.readbyqxmd.com/read/27932982/impact-of-cyp2c19-variants-on-clinical-efficacy-of-clopidogrel-and-1-year-clinical-outcomes-in-coronary-heart-patients-undergoing-percutaneous-coronary-intervention
#1
Hong Sun, Qiang Qu, Zhen-Fan Chen, Sheng-Lan Tan, Hai-Jun Zhou, Jian Qu, Hui Chen
The impact of pharmacogenetic variants of cytochrome P450 2C19 (CYP2C19) on clopidogrel-mediated effects on platelet inhibition, inflammatory response and endothelial function, as well as risk of major adverse cardiovascular events (MACE), in coronary heart patients undergoing percutaneous coronary intervention (PCI) was investigated. To this end, we assessed the residual platelet aggregation rate (RPA), maximal aggregation rate (MAR) and plasma levels of sCD40L, sP-selectin, MMP-9, sVCAM-1 and sE-selectin after 24 h of PCI in 559 patients treated with clopidogrel and followed up for 1 year for evidence of MACE...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27931206/survivalgwas_power-a-user-friendly-tool-for-power-calculations-in-pharmacogenetic-studies-with-time-to-event-outcomes
#2
Hamzah Syed, Andrea L Jorgensen, Andrew P Morris
BACKGROUND: Power calculators are currently available for the design of genetic association studies of binary phenotypes and quantitative traits, but not for "time to event" outcomes, which are of particular relevance in pharmacogenetics. With the rapid emergence of pharmacogenetic association studies of single nucleotide polymorphisms (SNPs), and the complexity of clinical outcomes they consider, there is a need for software to perform power calculations of time to event data over a range of design scenarios and analytical methodologies...
December 8, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/27928964/hot-topics-in-pharmacogenetics-of-age-related-macular-degeneration
#3
Stephen G Schwartz, Milam A Brantley, Jaclyn L Kovach, Andrzej Grzybowski
Age-related macular degeneration (AMD) is a leading cause of irreversible visual loss and is primarily treated with nutritional supplementation as well as with anti-vascular endothelial growth factor (VEGF) agents for certain patients with neovascular disease. AMD is a complex disease with both genetic and environmental risk factors. In addition, treatment outcomes from nutritional supplementation and anti-VEGF agents vary considerably. Therefore, it is reasonable to suspect that there may be pharmacogenetic influences on these treatments...
December 8, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27923663/pharmacogenetics-of-lithium-effects-on-glomerular-function-in-bipolar-disorder-patients-under-chronic-lithium-treatment-a-pilot-study
#4
Evangelia Eirini Tsermpini, Yanfei Zhang, Paola Niola, Caterina Chillotti, Raffaella Ardau, Alberto Bocchetta, George P Patrinos, Maria Del Zompo, Giovanni Severino, Ming Ta Michael Lee, Alessio Squassina
Bipolar disorder (BD) is a psychiatric disease characterized by alternating episodes of mania and depression. Lithium (Li) represents the mainstay treatment for BD, although a significant proportion of patients show insufficient or no response. Li is also associated with potentially severe side effects, including renal effects. Several studies reported that Li may induce reduction of glomerular filtration rate (GFR) in patients under long-term treatment. The biological systems and the genetic factors involved in susceptibility to Li-induced renal-side effects have been scarcely explored...
December 3, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27922550/a-novel-abcc6-haplotype-is-associated-with-azathioprine-drug-response-in-myasthenia-gravis
#5
Lara Colleoni, Barbara Galbardi, Claudia Barzago, Silvia Bonanno, Sara Franzi, Rita Frangiamore, Giorgia Camera, Maria Foti, Donatella Biancolini, Eleonora Canioni, Lorenzo Maggi, Carlo Antozzi, Renato Mantegazza, Pia Bernasconi, Dimos Kapetis
OBJECTIVE: We investigated the association of single nucleotide polymorphisms (SNPs) in drug-metabolizing enzymes and transporters (DMETs) with the response to azathioprine (AZA) in patients affected by myasthenia gravis (MG) to determine possible genotype-phenotype correlations. PATIENTS AND METHODS: Genomic DNA from 180 AZA-treated MG patients was screened through the Affymetrix DMET platform, which characterizes 1931 SNPs in 225 genes. The significant SNPs, identified to be involved in AZA response, were subsequently validated by allelic discrimination and direct sequencing...
December 2, 2016: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/27921434/-actual-trends-in-diagnostics-and-treatment-of-congenital-hyperinsulinism
#6
Juraj Staník, Martina Škopková, Monika Rosoľanková, Iwar Klimeš, Daniela Gašperíková
Congenital hyperinsulinism (CHI) is the most common cause of severe persistent hypoglycemia in neonates and infants. Early diagnosis and effective treatment (based on the principles of pharmacogenetics) play the key role for the prognosis. The DNA anlysis, which can identify mutation in one of the 11 genes causing MODY, is crutial in the diagnostics. Moreover, The genotype determines also the optimal therapy approach (medicaments, diet or rarely surgery). There was a large progress of novel medicaments treating particularly most severe (diazoxide-resistant) forms of CHI...
2016: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/27920888/development-of-a-high-resolution-melting-analysis-method-for-cyp2c19-17-genotyping-in-healthy-volunteers
#7
Zahra Ghasemi, Mehrdad Hashemi, Mahsa Ejabati, Seyyed Meisam Ebrahimi, Hamidreza Kheiri Manjili, Ali Sharafi, Ali Ramazani
BACKGROUND: Genetic polymorphisms of drug metabolisms by cytochrome P450 (P450s) could affect drug response, attracting particular interest in the pharmacogenetics. Due to the importance of CYP2C19* 17 allele and its capability of super- fast metabolism and also lack of information about distribution of the alleles in Iranian population, this research aimed to use High Resolution Melting (HRM) method compared to PCR-RFLP for genotyping healthy Iranian population. METHODS: Blood samples were collected from 100 healthy Iranian volunteers...
October 2016: Avicenna Journal of Medical Biotechnology
https://www.readbyqxmd.com/read/27918244/polymorphisms-of-abat-scn2a-and-aldh5a1-may-affect-valproic-acid-responses-in-the-treatment-of-epilepsy-in-chinese
#8
Xi Li, Jun Zhang, Xi Wu, Han Yan, Yin Zhang, Ruo-Hui He, Yong-Jun Tang, Yi-Jing He, Dan Tan, Xiao-Yuan Mao, Ji-Ye Yin, Zhao-Qian Liu, Hong-Hao Zhou, Jie Liu
AIM: The clinical efficacy of valproic acid (VPA) varies greatly among epileptic patients. To find the potential genetic factors related to VPA responses, the pharmacogenetics study was conducted. METHODS: Two hundred and one Chinese Han epileptic patients who were treated by VPA for at least 1 year were recruited. Up to 24 SNPs in 11 candidate genes that correlate with the metabolism, transport or target of VPA were genotyped. RESULTS: Three SNPs, rs1731017 (ABAT), rs2304016 (SCN2A) and rs1054899 (ALDH5A1) were found associated with VPA responses with the p-values of 0...
December 5, 2016: Pharmacogenomics
https://www.readbyqxmd.com/read/27913881/phase-ii-trial-of-s-1-plus-leucovorin-in-patients-with-advanced-gastric-cancer-and-clinical-prediction-by-s-1-pharmacogenetic-pathway
#9
Ming-Ming He, Dong-Sheng Zhang, Feng Wang, Zi-Xian Wang, Shu-Qiang Yuan, Zhi-Qiang Wang, Hui-Yan Luo, Chao Ren, Miao-Zhen Qiu, Ying Jin, De-Shen Wang, Dong-Liang Chen, Zhao-Lei Zeng, Yu-Hong Li, Yang-Yang He, Yuan-Tao Hao, Pi Guo, Feng-Hua Wang, Yi-Xin Zeng, Rui-Hua Xu
BACKGROUND: The first one-arm phase II trial aimed to evaluate and predict efficacy and safety of S-1 plus oral leucovorin (S-1/LV) as first-line chemotherapy for patients with advanced gastric cancer (AGC), using S-1 pharmacogenetic pathway approach. PATIENTS AND METHODS: A total of 39 patients orally took S-1 at conventional dose and LV simultaneously at a dose of 25 mg twice daily for a week, within a 2-week cycle. The primary endpoint was overall response rate (ORR), while the secondary endpoints were progression-free survival (PFS), time to failure (TTF), overall survival (OS), disease control rate (DCR), and adverse events (AEs)...
December 2, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27907852/the-relevance-of-primary-tumour-location-in-patients-with-metastatic-colorectal-cancer-a-meta-analysis-of-first-line-clinical-trials
#10
Julian Walter Holch, Ingrid Ricard, Sebastian Stintzing, Dominik Paul Modest, Volker Heinemann
BACKGROUND: Retrospective subgroup analyses suggest that primary tumour location (PTL) has a prognostic importance and relates to response to targeted therapy. METHODS: We conducted a meta-analysis of first-line clinical trials available up to October 2016, which assessed the relevance of PTL in patients with metastatic colorectal cancer (mCRC). Right- and left-sided colorectal cancers were differentiated (RC and LC). RESULTS: In 13 first-line randomised controlled trials and one prospective pharmacogenetic study, RC was associated with a significantly worse prognosis compared with LC (hazard ratio [HR] for overall survival: 1...
November 29, 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/27900781/the-present-and-future-of-opioid-analgesics-in-small-animal-practice
#11
REVIEW
B T Simon, P V Steagall
Opioids are the cornerstone for the treatment of acute pain in small animal patients. This is primarily because of their remarkable safety profile, high efficacy, and benefit of reversibility. There have been some significant advances in our knowledge on opioid pharmacology and clinical usage in companion animal medicine. This review discusses the progression of opioid use in small animal practice providing current misconceptions and controversies in light of routes of administration. Potential targets for research and drug development and novel therapies are discussed in addition to the concepts of glial cell modulators, individual variability, and opioid tolerance and hyperalgesia...
November 30, 2016: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27892694/gene-polymorphism-profiles-of-drug-metabolising-enzymes-gstm1-gstt1-and-gstp1-in-an-argentinian-population
#12
Natalia Weich, Alejandro Roisman, Belén Cerliani, Hilda V Aráoz, Lilien Chertkoff, Silvina M Richard, Irma Slavutsky, Irene B Larripa, Ariela F Fundia
BACKGROUND: Glutathione S-transferases (GSTs) are drug-metabolising enzymes involved in biotransformation of carcinogens, drugs, xenobiotics and oxygen free radicals. Polymorphisms of GST genes contribute to inter-individual and population variability in the susceptibility to environmental risk factors, cancer predisposition and pharmacotherapy responses. However, data about GST variability in Argentina are lacking. AIM: The purpose was to determine the prevalence of GSTM1, GSTT1 and GSTP1 polymorphisms in the general population from a central region of Argentina and to perform inter-population comparisons...
November 28, 2016: Annals of Human Biology
https://www.readbyqxmd.com/read/27889704/pharmacogenetic-studies-a-tool-to-improve-antidepressant-therapy
#13
Marta Ramos, Cecilia Berrogain, Julia Concha, Laura Lomba, Cristina Belén García, Mª Pilar Ribate
The World Health Organization (WHO) predicts that major depressive disorder (MDD) will be the second leading cause of death and disability by 2020. Nowadays, approximately 60-70% of patients with this disorder have shown the lack of effectiveness and tolerability of the therapy with antidepressants. The US Food and Drug Administration (FDA) and the European Medicine Agency (EMA) are including pharmacogenetic information in the labeling of several antidepressants. The presence of this information represents the relevance of genetic polymorphisms in drug response...
December 1, 2016: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/27878474/quantitative-assessment-of-cyp2c9-genetic-polymorphisms-effect-on-the-oral-clearance-of-s-warfarin-in-healthy-subjects
#14
Chanan Shaul, Simcha Blotnick, Mordechai Muszkat, Meir Bialer, Yoseph Caraco
BACKGROUND: Genetic polymorphisms in CYP2C9 account for 10-20% of the variability in warfarin dose requirement. As such CYP2C9 genetic polymorphisms are commonly included in algorithms aimed to optimize warfarin therapy as a way to account for variability in warfarin responsiveness that is due to altered pharmacokinetics. However, most of the currently available pharmacokinetic data were derived from studies among patients on chronic warfarin therapy and therefore suffer from the confounding effects of disease states and drug interactions...
November 22, 2016: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/27878470/%C3%AE-2-agonists
#15
Charlotte K Billington, Raymond B Penn, Ian P Hall
History suggests β agonists, the cognate ligand of the β2 adrenoceptor, have been used as bronchodilators for around 5,000 years, and β agonists remain today the frontline treatment for asthma and chronic obstructive pulmonary disease (COPD). The β agonists used clinically today are the products of significant expenditure and over 100 year's intensive research aimed at minimizing side effects and enhancing therapeutic usefulness. The respiratory physician now has a therapeutic toolbox of long acting β agonists to prophylactically manage bronchoconstriction, and short acting β agonists to relieve acute exacerbations...
November 23, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27875318/1846g-a-polymorphism-of-cyp2d6-gene-and-extrapyramidal-side-effects-during-antipsychotic-therapy-among-russians-and-tatars-a-pilot-study
#16
Dmitriy A Sychev, Irina S Burashnikova, Ruslan E Kazakov
BACKGROUND: Сytochrome P450 CYP2D6 activity affects antipsychotic therapy safety. 1846G>A (CYP2D6*4) polymorphism frequency varies among different ethnic groups. METHODS: We studied 1846G>A polymorphism in Tatar and Russian schizophrenic patients taking different antipsychotics and association of 1846G>A polymorphism and extrapyramidal disorders (EPD) frequency in schizophrenic patients on haloperidol monotherapy in daily doses up to 20 mg. RESULTS: Heterozygous 1846GA genotype frequency among Tatars was lower (23...
December 1, 2016: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/27865386/factors-associated-with-anti-tb-drug-induced-hepatotoxicity-and-genetic-polymorphisms-in-indigenous-and-non-indigenous-populations-in-brazil
#17
Melissa M Heinrich, Verônica M Zembrzuski, Marcos M Ota, Flavia P Sacchi, Raquel L F Teixeira, Pedro H Cabello Acero, Geraldo Marcelo Cunha, Reinaldo Souza-Santos, Julio Croda, Paulo C Basta
Anti-tuberculosis (TB) drugs are responsible for the occurrence of several adverse drug reactions (ADRs), including hepatotoxicity. The aim was to estimate the incidence of hepatotoxicity and its association with genetic polymorphisms and clinical-epidemiological factors by comparing indigenous and non-indigenous TB patients. We investigated clinical-epidemiological variables, serum levels of liver enzymes and NAT2, CYP2E1 and GSTM1 polymorphisms. A non-conditional logistic regression was used to identify the factors associated with hepatotoxicity...
December 2016: Tuberculosis
https://www.readbyqxmd.com/read/27864592/evaluation-of-5-fluorouracil-degradation-rate-and-pharmacogenetic-profiling-to-predict-toxicity-following-adjuvant-capecitabine
#18
Michela Roberto, Adriana Romiti, Andrea Botticelli, Federica Mazzuca, Luana Lionetto, Giovanna Gentile, Ida Paris, Rosa Falcone, Maria Bassanelli, Francesca Romana Di Pietro, Concetta Elisa Onesti, Elisabetta Anselmi, Serena Macrini, Maurizio Simmaco, Paolo Marchetti
BACKGROUND: On account of the lack of predictive biomarkers of toxicity, we investigated whether polymorphisms of genes involved in fluoropyrimidine metabolism and 5-fluorouracil (5-FU) degradation rate were associated with outcomes of adjuvant capecitabine in patients with early stage gastrointestinal cancers. METHODS: Genotyping of DPYD GIVS14A, MTHFR C677T and A1298C SNPs were performed by pyro-sequencing technology. PCR analysis was used for genotyping TYMS-TSER...
November 18, 2016: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27864383/use-of-pharmacogenetic-information-in-the-treatment-of-cardiovascular-disease
#19
REVIEW
Kevin Friede, Josephine Li, Deepak Voora
BACKGROUND: In 1964, Robert A. O'Reilly's research group identified members of a family who required remarkably high warfarin doses (up to 145 mg/day, 20 times the average dose) to achieve appropriate anticoagulation. Since this time, pharmacogenetics has become a mainstay of cardiovascular science, and genetic variants have been implicated in several fundamental classes of medications used in cardiovascular medicine. CONTENT: In this review, we discuss genetic variants that affect drug response to 3 classes of cardiovascular drugs: statins, platelet P2Y12 inhibitors, and anticoagulants...
November 18, 2016: Clinical Chemistry
https://www.readbyqxmd.com/read/27864209/pharmacists-should-jump-onto-the-clinical-pharmacogenetics-train
#20
Julie A Johnson
No abstract text is available yet for this article.
December 1, 2016: American Journal of Health-system Pharmacy: AJHP
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