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Cyp450 polymorphisms

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https://www.readbyqxmd.com/read/29629838/a-genetic-polymorphism-in-the-cyp1b1-gene-in-patients-with-squamous-cell-carcinoma-of-the-esophagus-an-iranian-mashhad-cohort-study-recruited-over-10-years
#1
Azam Rastgar Moghadam, Mehrane Mehramiz, Malihe Entezari, Hamideh Aboutalebi, Fatemeh Kohansal, Parisa Dadjoo, Hamid Fiuji, Mohammadreza Nasiri, Seyed Amir Aledavood, Kazem Anvari, Saeideh Ahmadi Simab, Mohammad Sadegh Khorrami, Ali Moradi, Seyed Mahdi Hassanian, Gordon A Ferns, Soodabeh Shahid Sales, Amir Avan
AIM: Esophageal cancer is the eighth most common cancer globally and the seventh most common cause of cancer-related deaths in men. Recent studies have shown that CYP450, family 1, subfamily B, polypeptide 1, which plays a role in the metabolism of xenobiotics, is associated with several cancers. Therefore, in the present study we investigated the association between a genetic variant, CYP1B1-rs1056836 gene, with the clinical characteristics of patients with squamous cell carcinoma of the esophagus (ESCC)...
April 9, 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29500141/polymorphisms-in-cyp450-genes-and-the-therapeutic-effect-of-atorvastatin-on-ischemic-stroke-a-retrospective-cohort-study-in-chinese-population
#2
Chen Peng, Ying Ding, Xin Yi, Yupei Shen, Zhiqiang Dong, Limei Cao, Qiang Li, Haiyan Ren, Lin He, Daizhan Zhou, Xu Chen
PURPOSE: Ischemic stroke (IS) is one of the most common neurologic diseases and is the main cause of death and disability in the Chinese population. This retrospective cohort study was performed to elucidate the relationship between single nucleotide polymorphisms (SNPs) in cytochrome P450 genes and the therapeutic effect of atorvastatin. METHODS: A total of 192 cases of IS were enrolled in the study. All patients were treated with atorvastatin, and their lipid levels and proportions were measured...
February 27, 2018: Clinical Therapeutics
https://www.readbyqxmd.com/read/29479969/detection-of-cytochrome-p450-polymorphisms-in-breast-cancer-patients-may-impact-on-tamoxifen-therapy
#3
Kanakaiah Thota, K Prasad, Mandava V Basaveswara Rao
Background: Breast cancer is the most common cancer among women worldwide. Tamoxifen (TAM), a selective estrogen receptor modulator, is widely used in its treatment. TAM is metabolized by cytochrome P450 (CYP450) enzymes, including CYP2D6, CYP3A5 and CYP2C19, whose genetic variations may have clinicopathological importance. However, reports on the association of various P450 polymorphisms with certain cancers are contradictory. Methods: We here investigated whether the prevalence of the four most common polymorphism in the CYP2D6*4 (G1934A), CYP2D6*10 (C188T), CYP3A5*3 and CYP2C19*2 alleles has any link with breast cancer using genomic DNA and polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis...
February 26, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/29464466/whichp450-a-multi-class-categorical-model-to-predict-the-major-metabolising-cyp450-isoform-for-a-compound
#4
Peter A Hunt, Matthew D Segall, Jonathan D Tyzack
In the development of novel pharmaceuticals, the knowledge of how many, and which, Cytochrome P450 isoforms are involved in the phase I metabolism of a compound is important. Potential problems can arise if a compound is metabolised predominantly by a single isoform in terms of drug-drug interactions or genetic polymorphisms that would lead to variations in exposure in the general population. Combined with models of regioselectivities of metabolism by each isoform, such a model would also aid in the prediction of the metabolites likely to be formed by P450-mediated metabolism...
February 20, 2018: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/29454235/donor-and-recipient-p450-gene-polymorphisms-influence-individual-pharmacological-effects-of-tacrolimus-in-chinese-liver-transplantation-patients
#5
Jianyu Liu, Yabo Ouyang, Dexi Chen, Bo Yao, Dongdong Lin, Zhiqiang Li, Yunjin Zang, Huan Liu, Xiaoyue Fu
The immunosuppressant drug tacrolimus (Tac) used for the prevention of immunological rejection is a metabolic substrate of cytochrome P450 enzymes. This study was designed to evaluate the short-term and long-term potential influence of single-nucleotide polymorphisms (SNPs) in CYP450 genes of liver transplant (LT) recipients as well as the donors on individual pharmacological effects of Tac and to guide individualized-medication from the perspective of pharmacogenomics. Twenty-one SNPs of the CYP450 gene were genotyped for both recipients and donors in 373 LT patients receiving Tac-based immunosuppressants...
April 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29439084/evaluating-the-impact-of-type-2-diabetes-mellitus-on-cyp450-metabolic-activities-protocol-for-a-case-control-pharmacokinetic-study
#6
Sophie Gravel, Jean-Louis Chiasson, Suzanne Dallaire, Jacques Turgeon, Veronique Michaud
INTRODUCTION: Diabetes affects more than 9% of the adult population worldwide. Patients with type 2 diabetes mellitus (T2DM) show variable responses to some drugs which may be due, in part, to variability in the functional activity of drug-metabolising enzymes including cytochromes P450 (CYP450s). CYP450 is a superfamily of enzymes responsible for xenobiotic metabolism. Knowledge must be gained on the impact of T2DM and related inflammatory processes on drug metabolism and its consequences on drug response...
February 8, 2018: BMJ Open
https://www.readbyqxmd.com/read/29385765/pharmacogenomic-impact-of-cyp2c19-variation-on-clopidogrel-therapy-in-precision-cardiovascular-medicine
#7
REVIEW
Sherry-Ann Brown, Naveen Pereira
Variability in response to antiplatelet therapy can be explained in part by pharmacogenomics, particularly of the CYP450 enzyme encoded by CYP2C19. Loss-of-function and gain-of-function variants help explain these interindividual differences. Individuals may carry multiple variants, with linkage disequilibrium noted among some alleles. In the current pharmacogenomics era, genomic variation in CYP2C19 has led to the definition of pharmacokinetic phenotypes for response to antiplatelet therapy, in particular, clopidogrel...
January 30, 2018: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29336255/fast-screening-technology-for-drug-emergency-management-predicting-suspicious-snps-for-adr-with-information-theory-based-models
#8
Zhaohui Liang, Jun Liu, Jimmy Xiangji Huang, Xing Zeng
OBJECTIVE: The genetic polymorphism of Cytochrome P450 (CYP 450) is considered as one of the main causes for adverse drug reactions (ADRs). In order to explore the latent correlations between ADRs and potentially corresponding single-nucleotide polymorphism (SNPs) in CYP450, three algorithms based on information theory are used as the main method to predict the possible relation. METHODS: The study uses a retrospective case-control study to explore the potential relation of ADRs to specific genomic locations and single-nucleotide polymorphism (SNP)...
January 14, 2018: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/29233455/genetic-variation-of-cytochrome-p450-in-uyghur-chinese-population
#9
Guangzhao Qi, Duolu Li, Xiaojian Zhang
Interindividual and interethnic variability of drug responses could be attributed to the differences of genetic polymorphisms in the drug metabolizing enzymes and transporters genes among the populations. Here we reviewed the studies of genetic variations in Uyghur Chinese of fifteen CYP450 genes including CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP2J2, CYP2W1, CYP3A4, CYP3A5, CYP4A11, and CYP17A1, which totally covered 277 variants. We also collected the data of 277 variants covered in our study in two extensive population sequencing projects, the International HapMap Project (Hap-Map) and the 1000 Genomes Project and compared them with the data of Uyghur Chinese...
February 2018: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29126801/species-differences-between-rat-and-human-in-vitro-metabolite-profile-in-vivo-predicted-clearance-cyp450-inhibition-and-cyp450-isoforms-that-metabolize-benzanthrone-implications-in-risk-assessment
#10
Isha Taneja, Kajal Karsauliya, Mamunur Rashid, Ashish Kumar Sonkar, Kanumuri Siva Rama Raju, Sandeep Kumar Singh, Mukul Das, Muhammad Wahajuddin, Sheelendra Pratap Singh
Benzanthrone (BNZ) is a polycyclic aromatic hydrocarbon found in industrial effluent causing skin, respiratory, gastrointestinal, genitourinary, nervous and hemopoietic toxicity. While its toxicity has been well studied, its metabolism in humans has not been investigated. The aim of this study was to characterize species differences in the in vitro metabolism of BNZ in rat and human liver microsomes and to identify the CYP isoforms involved in its metabolism. Upon incubation in liver microsomes, BNZ was found to be a direct substrate of phase I metabolism in both rat and human, undergoing oxidation and reduction...
January 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28960401/prediction-of-drug-drug-interactions-using-physiologically-based-pharmacokinetic-models-of-cyp450-modulators-included-in-simcyp-software
#11
Niloufar Marsousi, Jules A Desmeules, Serge Rudaz, Youssef Daali
In recent years, physiologically based PharmacoKinetic (PBPK) modeling has received growing interest as a useful tool for the assessment of drug pharmacokinetics. It has been demonstrated to be informative and helpful to quantify the modification in drug exposure due to specific physio-pathological conditions, age, genetic polymorphisms, ethnicity and particularly drug-drug interactions (DDIs). In this paper, the prediction success of DDIs involving various cytochrome P450 isoenzyme (CYP) modulators namely ketoconazole (a competitive inhibitor of CYP3A), itraconazole (a competitive inhibitor of CYP3A), clarithromycin (a mechanism-based inhibitor of CYP3A), quinidine (a competitive inhibitor of CYP2D6), paroxetine (a mechanism-based inhibitor of CYP2D6), ciprofloxacin (a competitive inhibitor of CYP1A2), fluconazole (a competitive inhibitor of CYP2C9/2C19) and rifampicin (an inducer of CYP3A) were assessed using Simcyp® software...
January 2018: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28934216/genetic-polymorphisms-of-cytochrome-p450-1a2-cyp1a2-among-emiratis
#12
Mohammad M Al-Ahmad, Naheed Amir, Subramanian Dhanasekaran, Anne John, Yousef M Abdulrazzaq, Bassam R Ali, Salim M A Bastaki
Cytochrome P450 1A2 (CYP1A2) is one of the CYP450 mixed-function oxidase system that is of clinical importance due to the large number of drug interactions associated with its induction and inhibition. In addition, significant inter-individual differences in the elimination of drugs metabolized by CYP1A2 enzyme have been observed which are largely due to the highly polymorphic nature of CYP1A2 gene. However, there are limited studies on CYP1A2 phenotypes and CYP1A2 genotypes among Emiratis and thus this study was carried out to fill this gap...
2017: PloS One
https://www.readbyqxmd.com/read/28927781/function-of-38-variants-cyp2c9-polymorphism-on-ketamine-metabolism-in%C3%A2-vitro
#13
Xiang Zheng, Ping Fang, Su-Su Bao, Dan Lin, Jian-Ping Cai, Guo-Xin Hu
BACKGROUND: Cytochrome P450 proteins (CYP 450) is the most important enzyme system of drug phase I metabolism in liver. In previous reports, reduced efficiency or increased risk of adverse events can be affected by primary sequence mutation in CYP450. AIM: To investigate the effect of gene polymorphism on the metabolism of ketamine in vitro, including the new alleles: 2C9*58, *59 and *60. METHOD: Incubation system which was contained insect microsome, b5, NADPH and 1M PBS incubated 10 μM-1000 μM ketamine in 37 °C for 40 min concentration of norketamine was analyzed by ultra-performance liquid chromatography-tandem mass spectrometry system (UPLC-MS/MS)...
September 1, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28920579/point-of-care-companion-diagnostic-tests-for-personalizing-psychiatric-medications-fulfilling-an-unmet-clinical-need
#14
Anil S Modak
Over the last decade stable isotope-labeled substrates have been used as probes for rapid, point-of-care, non-invasive and user-friendly phenotype breath tests to evaluate activity of drug metabolizing enzymes. These diagnostic breath tests can potentially be used as companion diagnostics by physicians to personalize medications, especially psychiatric drugs with narrow therapeutic windows, to monitor the progress of disease severity, medication efficacy and to study in vivo the pharmacokinetics of xenobiotics...
December 6, 2017: Journal of Breath Research
https://www.readbyqxmd.com/read/28873029/cyp450-genotype-phenotype-concordance-in-mexican-amerindian-indigenous-populations-where-to-from-here-for-global-precision-medicine
#15
Fernando de Andrés, Martha Sosa-Macías, Blanca Patricia Lazalde Ramos, María-Eugenia G Naranjo, Adrián LLerena
Global precision medicine demands characterization of drug metabolism and phenotype variation in diverse populations, including the indigenous societies. A related question is the extent to which CYP450 drug metabolizing enzyme genotype and phenotype data are concordant and whether they can be used interchangeably. These issues are increasingly debated as precision medicine continues to expand as a popular research topic worldwide. We report here the first study in clinically relevant CYP450 drug metabolism phenotypes and genotypes in Mexican Amerindian indigenous subjects...
September 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28603633/in-vitro-metabolism-of-exemestane-by-hepatic-cytochrome-p450s-impact-of-nonsynonymous-polymorphisms-on-formation-of-the-active-metabolite-17%C3%AE-dihydroexemestane
#16
Amity Peterson, Zuping Xia, Gang Chen, Philip Lazarus
Exemestane (EXE) is an endocrine therapy commonly used by postmenopausal women with hormone-responsive breast cancer due to its potency in inhibiting aromatase-catalyzed estrogen synthesis. Preliminary in vitro studies sought to identify phase I EXE metabolites and hepatic cytochrome P450s (CYP450s) that participate in EXE biotransformation. Phase I metabolites were identified by incubating EXE with HEK293-overexpressed CYP450s. CYP450s 1A2, 2C8, 2C9, 2C19, 2D6, 3A4, and 3A5 produce 17β-dihydroexemestane (17β-DHE), an active major metabolite, as well as two inactive metabolites...
June 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28592191/influence-of-two-variants-of-cyp450-oxidoreductase-on-the-stable-dose-of-acenocoumarol-in-a-spanish-population
#17
Hoi Y Tong, Alberto M Borobia, José Carlos Martínez Ávila, Rubin Lubomirov, Mario Muñoz, María J Blanco Bañares, Rafael Hernández, Carmen Fernández Capitán, Elena Ramírez, Jesús Frías, Antonio J Carcas
AIM: To evaluate the influence of two variants of P450 oxidoreductase (POR), rs2868177 and POR*28, on the stable dosage of acenocoumarol. PATIENTS & METHODS: For this observational, cross-sectional study, patients were undergone stable anticoagulant treatment with acenocoumarol. Univariate and multiple regression analyses were performed to assess the influence of POR polymorphisms. RESULTS: About 340 patients were enrolled. Multiple regression had a coefficient of determination (R(2)) of 51...
June 8, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28470107/cyp450-genotype-and-aggressive-behavior-on-selective-serotonin-reuptake-inhibitors
#18
Corine Ekhart, Maja Matic, Agnes Kant, Eugène van Puijenbroek, Ron van Schaik
AIM: Genetic variants for selective serotonin reuptake inhibitor (SSRI) metabolizing enzymes have been hypothesized to be a risk factor for aggression as adverse drug effect of SSRIs. Our aim was to assess the possible involvement of these polymorphisms on aggression when using SSRIs. MATERIALS & METHODS: A retrospective noninterventional case-control study was performed on 18 cases. The genetic profile of two main genes involved in the metabolism of SSRIs was determined, and predicted phenotype frequencies were compared with Dutch controls and literature data...
May 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28461741/functional-characterization-of-wild-type-and-24-cyp2d6-allelic-variants-on-gefitinib-metabolism-in-vitro
#19
Ping Fang, Xiang Zheng, Jiayang He, Honglei Ge, Pengfei Tang, Jianping Cai, Guoxin Hu
BACKGROUND: Cytochrome P450 2D6 (CYP2D6), a member of the CYP450 enzyme super family, is a polymorphic enzyme that metabolizes ~25% of therapeutic drugs. CYP2D6 exhibits significant genetic polymorphisms which might cause adverse effects and therapeutic failures of some drugs. OBJECTIVE: The purpose of this study was to evaluate the catalytic activities of 22 novel CYP2D6 alleles (CYP2D6*87, *88, *89, *90, *91, *92, *93, *94, *95, *96, *97, *98, R25Q, F164L, E215K, F219S, V327M, D336N, V342M, R344Q, R440C, R497C) on the metabolism of gefitinib in vitro...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28167220/omega-3-fatty-acids-and-cytochrome-p450-derived-eicosanoids-in-cardiovascular-diseases-which-actions-and-interactions-modulate-hemodynamics
#20
REVIEW
Sara Bonafini, Cristiano Fava
Increasing interest is focused on omega-3 fatty acids (FA) because of their potential beneficial effects, particularly in cardiovascular disease prevention. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), two major omega-3 FA, are mainly consumed through diet, particularly from fish and seafood intake, whereas alpha-linolenic acid (ALA) is present in high amounts in leafy green vegetables, nuts and seeds. The hypothesis of a cardiovascular protective action of omega-3 FA derives mainly from observational studies, whereas the evidence from interventional studies is not always consistent...
January 2017: Prostaglandins & Other Lipid Mediators
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