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Cyp450 polymorphisms

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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
#1
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
#2
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
#3
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 4, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28461741/functional-characterization-of-wild-type-and-24-cyp2d6-allelic-variants-on-gefitinib-metabolism-in-vitro
#4
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
#5
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
https://www.readbyqxmd.com/read/28046094/analysis-of-genetic-variation-in-cyp450-genes-for-clinical-implementation
#6
Liuh Ling Goh, Chia Wei Lim, Wey Cheng Sim, Li Xian Toh, Khai Pang Leong
BACKGROUND: Genetic determinants of drug response remain stable throughout life and offer great promise to patient-tailored drug therapy. The adoption of pharmacogenetic (PGx) testing in patient care requires accurate, cost effective and rapid genotyping with clear guidance on the use of the results. Hence, we evaluated a 32 SNPs panel for implementing PGx testing in clinical laboratories. METHODS: We designed a 32-SNP panel for PGx testing in clinical laboratories...
2017: PloS One
https://www.readbyqxmd.com/read/27942916/synergistic-disruption-of-er%C3%AE-her2-crosstalk-by-endoxifen-and-lapatinib-in-breast-cancer-cells
#7
James Chun Yip Chan, Pei Shi Ong, Peirong Lim, Preben Xiang Long Teng, Eric Chun Yong Chan
BACKGROUND: Despite decades of clinical success, tamoxifen therapy is complicated by inter-individual variability due to CYP450 polymorphism and resistance attributed to ERα/HER2 crosstalk. Direct administration of endoxifen shows promise in circumventing obligatory CYP450 bioactivation while maintaining efficacy. Separately, disruption of the crosstalk using probe antagonists against ERα (tamoxifen) and HER2 (e.g., lapatinib) has been explored clinically. However, the efficacy of this combination may be confounded by lapatinib, a potent inactivator of CYP3A4/5 which could negate the bioactivation of tamoxifen to the active metabolite endoxifen...
January 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27925256/pharmacokinetic-drug-drug-interactions-of-tyrosine-kinase-inhibitors-a-focus-on-cytochrome-p450-transporters-and-acid-suppression-therapy
#8
REVIEW
Caroline Gay, Delphine Toulet, Pascal Le Corre
The extensive use of tyrosine kinase inhibitors (TKI's) in hematology and oncology has shown that these drugs have a significant potential for drug-drug interactions. Since these drugs have a rather low therapeutic window, some drug interactions are of particular clinical relevance either on drug toxicity or on patient's response. Significant interactions occur with concomitant use of acid-suppressive therapy leading to a decreased oral bioavailability. However, such interactions are drug dependent according to their solubility pattern and to the duration of action of acid-suppressive therapy, which is coprescribed...
December 7, 2016: Hematological Oncology
https://www.readbyqxmd.com/read/27919191/phytotherapeutic-approach-a-new-hope-for-polycyclic-aromatic-hydrocarbons-induced-cellular-disorders-autophagic-and-apoptotic-cell-death
#9
REVIEW
Durgesh Nandini Das, Prashanta Kumar Panda, Prajna Paramita Naik, Subhadip Mukhopadhyay, Niharika Sinha, Sujit K Bhutia
Polycyclic aromatic hydrocarbons (PAHs) comprise the major class of cancer-causing chemicals and are ranked ninth among the chemical compounds threatening to humans. Moreover, interest in PAHs has been mainly due to their genotoxic, teratogenic, mutagenic and carcinogenic property. Polymorphism in cytochrome P450 (CYP450) and aryl hydrocarbon receptor (AhR) has the capacity to convert procarcinogens into carcinogens, which is an imperative factor contributing to individual susceptibility to cancer development...
January 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/27767381/the-effect-of-snps-in-cyp450-in-chloroquine-primaquine-plasmodium-vivax-malaria-treatment
#10
Vinicius A Sortica, Juliana D Lindenau, Maristela G Cunha, Maria DO Ohnishi, Ana Maria R Ventura, Ândrea Kc Ribeiro-Dos-Santos, Sidney Eb Santos, Luciano Sp Guimarães, Mara H Hutz
BACKGROUND: Chloroquine/primaquine is the current therapy to eliminate Plasmodium vivax infection in the Amazon region. AIMS: This study investigates CYP1A2, CYP2C8, CYP2C9, CYP3A4 and CYP3A5 genetic polymorphisms influence on cloroquine/primaquine treatment. PATIENTS & METHODS: Generalized estimating equations analyses were performed to determine the genetic influence in parasitemia and/or gametocytemia clearance over treatment time in 164 patients...
October 21, 2016: Pharmacogenomics
https://www.readbyqxmd.com/read/27732553/rapid-screening-for-targeted-genetic-variants-via-high-resolution-melting-curve-analysis
#11
Allison B Chambliss, Molly Resnick, Athena K Petrides, William A Clarke, Mark A Marzinke
BACKGROUND: Current methods for the detection of single nucleotide polymorphisms (SNPs) associated with aberrant drug-metabolizing enzyme function are hindered by long turnaround times and specialized techniques and instrumentation. In this study, we describe the development and validation of a high-resolution melting (HRM) curve assay for the rapid screening of variant genotypes for targeted genetic polymorphisms in the cytochrome P450 enzymes CYP2C9, CYP2C19, and CYP3A5. METHODS: Sequence-specific primers were custom-designed to flank nine SNPs within the genetic regions of aforementioned drug metabolizing enzymes...
March 1, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/27515451/cyp2b6-and-oprm1-receptor-polymorphisms-at-methadone-clinics-and-novel-oprm1-haplotypes-a-cross-sectional-study
#12
Ahmad Abdulrahman AlMeman, Rusli Ismail, Markus Perola
INTRODUCTION: Methadone is accepted as an alternative therapy in opioid use disorders worldwide. Methadone responsiveness, however, is affected by a range of CYP450 enzymes and OPRM1 polymorphisms. OBJECTIVE: This study sought to detect CYP2B6 and OPRM1 variants and their genotypes, as major contributors to inter-variability in methadone responsiveness and methadone dose requirements. METHODS: We carried out a prospective experimental one-phase pharmacogenetic study in four addiction clinics in Malaysia...
2016: Drug Metabolism Letters
https://www.readbyqxmd.com/read/27509973/roles-of-cyp1a1-and-cyp2e1-gene-polymorphisms-in-oral-submucous-fibrosis
#13
Punyo Yaming, Aadithya Basavaraj Urs, Alpana Saxena, Mariyam Zuberi
Oral submucous fibrosis (OSF) is a precancerous condition with a 4 to13% malignant transformation rate. Related to the habit of areca nut chewing it is mainly prevalent in Southeast Asian countries where the habit of betel quid chewing is frequently practised. On chewing, alkaloids and polyphenols are released which undergo nitrosation and give rise to Nnitrosamines which are cytotoxic agents. CYP450 is a microsomal enzyme group which metabolizes various endogenous and exogenous chemicals including those released by areca nut chewing...
2016: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/27432796/cyp2c19-genotype-dependent-pharmacokinetic-drug-interaction-between-voriconazole-and-ritonavir-boosted-atazanavir-in-healthy-subjects
#14
Li Zhu, Roger J Brüggemann, Jonathan Uy, Angela Colbers, Matthew W Hruska, Ellen Chung, Karen Sims, Blisse Vakkalagadda, Xiaohui Xu, Ron H N van Schaik, David M Burger, Richard J Bertz
Voriconazole, a broad-spectrum triazole antifungal agent, is metabolized by cytochrome P450 (CYP) 2C19 and, to a lesser extent, by CYP3A. Genetic polymorphism of CYP2C19 not only plays a prominent role in its disposition but may also influence potential drug interactions with CYP450 modulators such as ritonavir. This study assessed 2-way drug interactions of voriconazole added on to ritonavir-boosted atazanavir in both CYP2C19 extensive-metabolizer (EM) and poor-metabolizer (PM) healthy subjects. Each subject received voriconazole alone on days 1-3, followed by a 7-day washout...
February 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27388970/the-role-of-cytochrome-p450-pharmacogenomics-in-chronic-non-cancer-pain-patients
#15
Tatiana Tverdohleb, Bora Dinc, Ivana Knezevic, Kenneth D Candido, Nebojsa Nick Knezevic
INTRODUCTION: Pharmacogenomics is the field that studies an individualized treatment approach for patients' medication regimen that can impact drug safety, productivity, and personalized health care. Pharmacogenomics characterizes the genetic differences in metabolic pathways which can affect a patient's individual responses to drug treatments. AREAS COVERED: The various responses to pharmacological agents are mainly determined by the different types of genetic variants of the CYP450...
July 15, 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27281544/mechanisms-of-interaction-between-persistent-organic-pollutants-pops-and-cyp2b6-an-in-silico-approach
#16
Wilson Maldonado-Rojas, Karen Rivera-Julio, Jesus Olivero-Verbel, Diana S Aga
Human Cytochrome P450s (CYP450) are a group of heme-containing metalloenzymes responsible for recognition and metabolism of numerous xenobiotics, including drugs and environmental contaminants. CYP2B6, a member of CYP450, is well known for being a highly inducible and polymorphic enzyme and for its important role in the oxidative metabolism of environmental pollutants, such as the Polybrominated Diphenyl Ethers (PBDEs) and Polychlorinated Biphenyls (PCBs). However the mechanisms of interaction of PBDEs and PCBs with CYP2B6 is not entirely known...
September 2016: Chemosphere
https://www.readbyqxmd.com/read/27199033/effects-of-cyp2c19-variants-on-methadone-metabolism-in-vitro
#17
Tian Lan, Ling-Jing Yuan, Xiao-Xia Hu, Quan Zhou, Jun Wang, Xiang-Xin Huang, Da-Peng Dai, Jian-Ping Cai, Guo-Xin Hu
CYP2C19 is an important member of the cytochrome P450 (CYP450) enzyme super family and is responsible for clearing approximately 10% of commonly used clinical drugs that undergo phase I metabolism. Genetic polymorphisms of CYP2C19 significantly influence the efficacy and safety of some drugs, which might cause undesirable adverse effects or cure failure at standard dosages. The aim of this study was to clarify the catalytic activities of 31 CYP2C19 alleles on the oxidative in vitro metabolism of methadone. Insect microsomes expressing the CYP2C19 alleles were incubated with 50-2000 μM methadone for 30 min at 37 °C and terminated by cooling to -80 °C immediately...
April 2017: Drug Testing and Analysis
https://www.readbyqxmd.com/read/27141907/-research-progress-of-the-gene-polymorphisms-of-metabolic-enzyme-related-to-polycyclic-aromatic-hydrocarbons-risk-of-preterm-birth
#18
N Liu, Z W Li
The etiology and underlying biological mechanisms for preterm birth are relatively intricate, involving both genetic and environmental factors. Therefore, in the process of research on environmental factors of preterm birth, individual genetic susceptibility is an important aspect which cannot be ignored. Detoxification and metabolism abilities of enzymes to the environmental toxins is determined by their genetic polymorphism, which directly affect the toxic effects of poison. The measurement of gene polymorphisms related to metabolic enzymes may have important significance in the research of biological mechanisms, the risk prediction for preterm birth and the development of the preventive measures...
May 2016: Zhonghua Yu Fang Yi Xue za Zhi [Chinese Journal of Preventive Medicine]
https://www.readbyqxmd.com/read/27010727/genome-wide-pharmacogenomic-study-on-methadone-maintenance-treatment-identifies-snp-rs17180299-and-multiple-haplotypes-on-cyp2b6-spon1-and-gsg1l-associated-with-plasma-concentrations-of-methadone-r-and-s-enantiomers-in-heroin-dependent-patients
#19
Hsin-Chou Yang, Shih-Kai Chu, Chieh-Liang Huang, Hsiang-Wei Kuo, Sheng-Chang Wang, Sheng-Wen Liu, Ing-Kang Ho, Yu-Li Liu
Methadone maintenance treatment (MMT) is commonly used for controlling opioid dependence, preventing withdrawal symptoms, and improving the quality of life of heroin-dependent patients. A steady-state plasma concentration of methadone enantiomers, a measure of methadone metabolism, is an index of treatment response and efficacy of MMT. Although the methadone metabolism pathway has been partially revealed, no genome-wide pharmacogenomic study has been performed to identify genetic determinants and characterize genetic mechanisms for the plasma concentrations of methadone R- and S-enantiomers...
March 2016: PLoS Genetics
https://www.readbyqxmd.com/read/26968424/in-vitro-assessment-of-24-cyp2d6-allelic-isoforms-on-the-metabolism-of-methadone
#20
Ying Su, Yun-Yun Zhan, Ben-Fu Wang, Si-Cong Wang, Da-Peng Dai, Guo-Xin Hu, Han Lin, Qing-Quan Lian, Jian-Ping Cai
CYP2D6 is an important member of the cytochrome P450 (CYP450) enzyme super family, with at least 100 CYP2D6 alleles being previously identified. Genetic polymorphisms of CYP2D6 significantly influence the efficacy and safety of some drugs, which might cause adverse effects and therapeutic failure. The aim of this study was to clarify the catalytic activities of 24 CYP2D6 alleles on the oxidative in vitro metabolism of methadone. Reactions were incubated with 50-2000  µM methadone for 30 min at 37 °C and terminated by cooling to -80 °C immediately...
February 2017: Drug Testing and Analysis
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