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Cyp450 polymorphisms

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
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...
October 12, 2016: Clinical Chemistry and Laboratory Medicine: CCLM
Ahmad Abdulrahman Almeman, R 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...
August 10, 2016: Drug Metabolism Letters
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
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...
July 19, 2016: Journal of Clinical Pharmacology
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
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
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...
May 19, 2016: Drug Testing and Analysis
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]
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
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...
March 9, 2016: Drug Testing and Analysis
Manjul Rana, Suneeta Devi, Samudrala Gourinath, Ravinder Goswami, Rakesh K Tyagi
Pregnane & Xenobiotic Receptor (PXR) acts as a xenosensing transcriptional regulator of many drug metabolizing enzymes and transporters of the 'detoxification machinery' that coordinate in elimination of xenobiotics and endobiotics from the cellular milieu. It is an accepted view that some individuals or specific populations display considerable differences in their ability to metabolize different drugs, dietary constituents, herbals etc. In this context we speculated that polymorphisms in PXR gene might contribute to variability in cytochrome P450 (CYP450) metabolizing enzymes of phase I, drug metabolizing components of phase II and efflux components of the detoxification machinery...
September 2016: Biochimica et Biophysica Acta
Jan Henrik Schirmer, Jan Phillip Bremer, Frank Moosig, Julia Ulrike Holle, Peter Lamprecht, Stefan Wieczorek, Sierk Haenisch, Ingolf Cascorbi
AIM: Correlation of outcomes of cyclophosphamide (CP) therapy in antineutrophil cytoplasmic antibody-associated vasculitis with genotype polymorphisms in prodrug activating cytochrome P450 enzyme genes CYP2C9 and CYP2C19. PATIENTS & METHODS: One hundred and ninety six patients with antineutrophil cytoplasmic antibody-associated vasculitis treated with CP, either as intravenous pulse or as daily oral medication, were included. Genotypes of CYP2C9 and CYP2C19 were correlated with clinical outcomes (leukopenia, infection, urotoxicity and treatment response)...
March 2016: Pharmacogenomics
Ian R McGrane, Joshua G Loveland
OBJECTIVE: The cytochrome P450 (CYP450) enzyme system metabolizes many psychiatric medications. We compare frequencies of alleles and phenotypes for CYP2D6, CYP2C9, and CYP2C19 in American Indian (AI) and Caucasian youth treated at a psychiatric hospital in the Northwestern United States. METHODS: A retrospective chart review evaluated CYP450 pharmacogenetic (PGx) data from the Shodair Children's Hospital Clinical Genetic Laboratory between 2006 and 2014. CYP2D6 genotyping was performed using the xTAG® CYP2D6 Kit (Luminex, Austin, TX)...
May 2016: Journal of Child and Adolescent Psychopharmacology
Xingyang Yi, Duanxiu Liao, Lang Wu, Hong Chen, Jie Li, Chun Wang
AIM: To evaluate the relationship between CYP genetic polymorphisms and CYP metabolite levels with carotid artery stenosis in acute ischemic stroke (IS) patients. METHODS: Eleven single nucleotide polymorphisms (SNPs) of seven CYP genes were genotyped in 136 IS patients with carotid stenosis and 158 patients without carotid stenosis. CYP plasma metabolite levels [20-hydroxyeicosatetraenoic acid (HETE), total epoxyeicosatrienoic acids (EETs), and dihydroxyeicosatrienoic acids (DiHETEs)] were assessed in a subsample of 90 patients with carotid stenosis and 96 patients without carotid stenosis...
May 2, 2016: Journal of Atherosclerosis and Thrombosis
Xin He, Shan Feng
Cytochrome P450 (CYP450) enzymes are the most important metabolizing enzyme family exists among all organs. Apart from their role in the deactivation of most endogenous compounds and xenobiotics, they also mediate most procarcinogens oxidation to ultimate carcinogens. There are several modes of CYP450s activation of procarcinogens. 1) Formation of epoxide and diol-epoxides intermediates, such as CYP1A1 and CYP1B1 mediates PAHs oxidation to epoxide intermediates; 2) Formation of diazonium ions, such as CYP2A6, CYP2A13 and CYP2E1 mediates activation of most nitrosamines to unstable metabolites, which can rearrange to give diazonium ions...
2015: Current Drug Metabolism
Hanna K Flaten, Howard S Kim, Jenny Campbell, Lisa Hamilton, Andrew A Monte
BACKGROUND: CYP450 polymorphisms result in variable rates of drug metabolism. CYP drug-drug interactions can contribute to altered drug effectiveness and safety. STUDY OBJECTIVES: The primary objective was to determine the percentage of emergency department (ED) patients with cytochrome 2C19 (CYP2C19) drug-drug interactions. The secondary objective was to determine the prevalence of CYP2C19 polymorphisms in a US ED population. METHODS: We conducted a prospective observational study in an urban academic ED with 72,000 annual visits...
February 2016: American Journal of Emergency Medicine
Gaurav Agarwal, Sonam Tulsyan, Punita Lal, Balraj Mittal
BACKGROUND: Prediction of response and toxicity of chemotherapy can help personalize the treatment and choose effective yet non-toxic treatment regimen for a breast cancer patient. Interplay of variations in various drug-metabolizing enzyme (DME)-encoding genes results in variable response and toxicity of chemotherapeutic drugs. Generalized multi-analytical (GMDR) approach was used to determine the influence of the combination of variants of genes encoding phase 0 (SLC22A16); phase I (CYP450, NQO1); phase II (GSTs, MTHFR, UGT2B15); and phase III (ABCB1) DMEs along with confounding factors on the response and toxicity of chemotherapeutic drugs in breast cancer patients...
July 2016: World Journal of Surgery
Xing-Yang Yi, Duan-Xiu Liao, Chun Wang, Wen Cheng, Xiu-Quan Fu, Biao Zhang
AIM: Cytochrome P450s (CYP450) enzymes regulate inflammation and atherosclerosis and can affect carotid plaque stability in patients with ischemic stroke (IS). This study aimed to investigate the association of CYP450 genetic variants with CYP plasma metabolite levels and plaque stability in patients with IS. METHODS: Eleven single nucleotide polymorphisms (SNPs) of CYP genes and their plasma metabolite [20-hydroxyeicosatetraenoic acid (HETE), total epoxyeicosatrienoic acids (EETs), and dihydroxyeicosatrienoic acids (DiHETEs)] levels were measured in 396 patients with IS who underwent high-resolution B-mode ultrasound carotid plaque detection and were stratified into the following groups: non-carotid plaque and carotid plaque groups...
2016: Journal of Atherosclerosis and Thrombosis
Li-qun Chi, Xin Lu, Lei Wang, Shu-ping Liu, Nan Ding, Hong-ying Zhang, Wen E
OBJECTIVE: To investigate the relationship between single nucleotide polymorphisms (SNPs) of cytochrome P450 (CYP450) 3A4 rs2242480 and inter-individual differences of sufentanil consumption in accouchement sans douleur. METHODS: A total of 131 parturient women were collected. According to the distribution of genotypes and allele frequencies of rs2242480, the doses of sufentanil were individually designed. CC homozygotes were given the standard analgesia dose, CT heterozygotes and TT homozygotes were given 87...
August 18, 2015: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
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