249 results match your criteria genotyping ugt1a1


Elucidating the role of pharmacogenetics in irinotecan efficacy and adverse events in metastatic colorectal cancer patients.

Expert Opin Drug Metab Toxicol 2021 Sep 6:1-7. Epub 2021 Sep 6.

U705, Isciii Center for Biomedical Research on Rare Diseases (Ciberer), Barcelona, Spain.

Introduction: Irinotecan is a cytotoxic agent that is widely used in the treatment of several types of solid tumors. However, although it is generally well tolerated, approximately 20% to 35% of patients develop severe toxicity, particularly delayed-type diarrhea and neutropenia. As the incidence of such toxicities is often associated with the and genotypes, individualized dosing could reduce these adverse events. Read More

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September 2021

Associations between Polymorphisms in Phase II Enzymes and Circulating Sex-Steroid Hormones in White Postmenopausal Women.

J Menopausal Med 2021 Aug;27(2):79-86

Department of Food Science and Nutrition, University of Minnesota, St. Paul, MN, USA.

Objectives: The purpose of this cross-sectional study was to examine whether single nucleotide polymorphisms (SNPs) in enzymes that metabolize sex steroid hormones were associated with the blood levels of these hormones in postmenopausal women and if the use of menopausal hormone therapy (MHT) could modify this association.

Methods: Baseline data were collected from 932 postmenopausal women enrolled in the Minnesota Green Tea Trial. Participants filled out a questionnaire about their demographics, lifestyle factors, and medical and reproductive history. Read More

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Analytical validation of a laboratory-development multigene pharmacogenetic assay.

Pharmacogenet Genomics 2021 Oct;31(8):177-184

Pharmacogenetic Laboratory, Genetics Department, Hospital Universitario La Paz.

Objective: The implementation of pharmacogenetics (PGx) in clinical practice is an essential tool for personalized medicine. However, clinical laboratories must validate their procedures before being used to perform PGx studies in patients, in order to confirm that they are adequate for the intended purposes.

Methods: We designed a validation process for our in-house pharmacogenetic PCR-based method assay. Read More

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October 2021

TaqMan real time PCR for the Detection of the Gilbert's Syndrome Markers UGT1A1*28; UGT1A1*36 and UGT1A1*37.

Mol Biol Rep 2021 May 4;48(5):4953-4959. Epub 2021 Jun 4.

Department of Public Health and Pediatrics, School of Medicine, University of Turin, Piazza Polonia 94, 10126, Turin, Italy.

Gilbert's syndrome is characterized by mild unconjugated hyperbilirubinemia. The key of this disease is a diminished activity of UDP-glucuronosyltransferase 1A1 (UGT1A1). TA insertion into the TATA box promoter region of the UGT1A1 gene on chromosome 2 is the genetic basis of Gilbert's syndrome (UGT1A1*28). Read More

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Dexketoprofen Pharmacokinetics is not Significantly Altered by Genetic Polymorphism.

Front Pharmacol 2021 29;12:660639. Epub 2021 Apr 29.

Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teófilo Hernando, Universidad Autónoma de Madrid (UAM), Instituto de Investigación Sanitaria La Princesa (IP), Madrid, Spain.

Dexketoprofen is the (S)-(+)-enantiomer of racemic ketoprofen, a nonsteroidal anti-inflammatory drug used for the management of different types of pain. To the best of our knowledge, no article was published to date on dexketoprofen pharmacogenetics. Thence, in this work, we aimed to explore the influence of sex, race and several single nucleotide polymorphisms (SNPs) in genes encoding metabolizing enzymes (e. Read More

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Polymorphism for Irinotecan Dose Escalation in Patients with -Mutated Metastatic Colorectal Cancer Treated with First-Line Bevacizumab and FOLFIRI.

J Oncol 2021 9;2021:6686517. Epub 2021 Mar 9.

Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

Background: Patients with metastatic colorectal cancer (mCRC) and V600E mutation have a poor prognosis, with a median progression-free survival (PFS) of only 5-7 months after initial therapy. The current standard first-line chemotherapy for these patients includes FOLFOX or FOLFIRI plus bevacizumab. In this study, we explored the effects and oncological outcomes of polymorphism for irinotecan escalation in patients with mutated mCRC. Read More

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UGT1A1 Gene Polymorphisms in Patients with Small Cell Lung Cancer Treated with Irinotecan-Platinum Doublet Chemotherapy and Their Association with Gastrointestinal Toxicity and Overall Survival.

Oncologist 2021 Aug 12;26(8):701-713. Epub 2021 Apr 12.

Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

Background: Irinotecan (CPT11) is an important drug for small cell lung cancer (SCLC) chemotherapy (CTx). UDP-glucuronosyltransferase 1A1 (UGT1A1) polymorphisms can influence CPT11-related toxicity. This study aimed to assess prevalence of UGT1A1 polymorphisms and their association with clinical outcomes in patients with SCLC on CPT11-CTx. Read More

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Identification of Novel UGT1A1 Variants Including UGT1A1 454C>A through the Genotyping of Healthy Participants of the HPTN 077 Study.

ACS Pharmacol Transl Sci 2021 Feb 21;4(1):226-239. Epub 2021 Jan 21.

Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, United States.

Cabotegravir (CAB) is an integrase strand-transfer inhibitor of HIV that has proven effective for HIV treatment and prevention in a long-acting injectable formulation, typically preceded by an oral formulation lead-in phase. Previous studies have demonstrated that CAB is primarily metabolized via glucuronidation by uridine diphosphate glucuronosyltransferase (UGT) 1A1 and 1A9. In this study, we performed next-generation sequencing of genomic DNA isolated from the HPTN 077 participants to explore the variants within and . Read More

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February 2021

Pharmacogenetics Guidelines: Overview and Comparison of the DPWG, CPIC, CPNDS, and RNPGx Guidelines.

Front Pharmacol 2020 25;11:595219. Epub 2021 Jan 25.

Division of Laboratories, Pharmacy, and Biomedical Genetics, Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht, Netherlands.

Many studies have shown that the efficacy and risk of side effects of drug treatment is influenced by genetic variants. Evidence based guidelines are essential for implementing pharmacogenetic knowledge in daily clinical practice to optimize pharmacotherapy of individual patients. A literature search was performed to select committees developing guidelines with recommendations being published in English. Read More

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January 2021

Implementation of pharmacogenomic testing in oncology care (PhOCus): study protocol of a pragmatic, randomized clinical trial.

Ther Adv Med Oncol 2020 17;12:1758835920974118. Epub 2020 Dec 17.

Section of Hematology/Oncology, Department of Medicine, University of Chicago Medical Center and Biological Sciences, Chicago, 5841 S. Maryland Avenue, MC2115, Chicago, IL 60637, USA.

Background: Many cancer patients who receive chemotherapy experience adverse drug effects. Pharmacogenomics (PGx) has promise to personalize chemotherapy drug dosing to maximize efficacy and safety. Fluoropyrimidines and irinotecan have well-known germline PGx associations. Read More

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December 2020

PharmFrag: An Easy and Fast Multiplex Pharmacogenetics Assay to Simultaneously Analyze 9 Genetic Polymorphisms Involved in Response Variability of Anticancer Drugs.

Int J Mol Sci 2020 Dec 17;21(24). Epub 2020 Dec 17.

IRSET (Institut de Recherche en Santé, Environnement et Travail), University of Rennes, CHU Rennes, EHESP, UMR_S 1085, 35000 Rennes, France.

Regarding several cytotoxic agents, it was evidenced that genetic polymorphisms in genes encoding enzymes involved in their metabolism are associated with higher risk of toxicity. Genotyping these genes before treatment is a valuable strategy to prevent side effects and to predict individual response to drug therapy. This pharmacogenetic approach is recommended for chemotherapies such as thiopurines (azathioprine, 6-mercaptopurine, thioguanine), irinotecan, and fluoropyrimidines (capecitabine and 5-fluorouracil). Read More

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December 2020

Pre-therapeutic UGT1A1 genotyping to reduce the risk of irinotecan-induced severe toxicity: Ready for prime time.

Eur J Cancer 2020 12 23;141:9-20. Epub 2020 Oct 23.

Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands. Electronic address:

Background: Pre-therapeutic UGT1A1 genotyping is not yet routinely performed in most hospitals in patients starting irinotecan chemotherapy. The aim of this position paper was to evaluate the available evidence and to assess the potential value of genotyping of UGT1A1∗28 and UGT1A1*6 in patients before starting treatment with irinotecan to reduce the risk of severe toxicity.

Methods: The literature was selected and assessed based on five pre-specified criteria: 1) the level of evidence for associations between UGT1A1 polymorphisms and irinotecan-induced severe toxicity, 2) clinical validity and utility of pre-therapeutic genotyping of UGT1A1, 3) safety and tolerability of irinotecan in carriers of UGT1A1 polymorphisms, 4) availability of specific dose recommendations for irinotecan in carriers of UGT1A1 polymorphisms, 5) evidence of cost benefits of pre-therapeutic genotyping of UGT1A1. Read More

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December 2020

Determination of the UGT1A1 polymorphism as guidance for irinotecan dose escalation in metastatic colorectal cancer treated with first-line bevacizumab and FOLFIRI (PURE FIST).

Eur J Cancer 2020 10 20;138:19-29. Epub 2020 Aug 20.

Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address:

Aim: Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) polymorphism plays a crucial role in the increased susceptibility of patients to irinotecan and its toxicity. This study is a multicenter, randomised clinical trial comparing the clinical outcomes and adverse events (AEs) in metastatic colorectal cancer (mCRC) patients treated with bevacizumab plus FOLFIRI with or without UGT1A1 genotyping and irinotecan dose escalation as the first-line therapy.

Methods: The control group received conventional biweekly FOLFIRI plus bevacizumab without UGT1A1 genotyping, whereas the study group received the same regimen with irinotecan dose escalation based on UGT1A1 genotyping. Read More

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October 2020

Effect of Mutations on mRNA and Globin Stability: The Cases of Hb Bernalda/Groene Hart and Hb Southern Italy.

Genes (Basel) 2020 07 31;11(8). Epub 2020 Jul 31.

Institute of Genetics and Biophysics "Adriano Buzzati Traverso", (IGB-ABT, CNR), National Research Council, 80131 Naples, Italy.

We identified two unstable variants in the third exon of α-globin genes: Hb Bernalda/Groene Hart (HBA1:c.358C>T), and Hb Caserta (HBA2:c.79G>A) in to Hb Sun Prairie (HBA2:c. Read More

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Genetic Variants as Predictors of Irinotecan-Induced Severe Gastrointestinal Toxicity in Metastatic Colorectal Cancer Patients.

Front Pharmacol 2020 30;11:973. Epub 2020 Jun 30.

Medical Oncology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.

Irinotecan is widely used in the treatment of metastatic colorectal cancer (mCRC) despite its severe toxicities. Toxicity is often associated with the genotype. An explanation for idiopathic toxicity beyond the biomarker, however, remains a major concern for clinicians. Read More

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Genetic and clinical risk factors associated with phenytoin-induced cutaneous adverse drug reactions in Thai population.

Pharmacoepidemiol Drug Saf 2020 05 5;29(5):565-574. Epub 2020 Mar 5.

Clinical Pharmacy Division, Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.

Objective: This study aimed to describe the genetic and clinical risk factors associated with phenytoin-induced cutaneous adverse drug reactions (PHT-induced cADRs) in Thai patients.

Method: A retrospective case-control study was conducted among 88 PHT- cADRs (25 SJS/TEN, 37 DRESS/DIHS and 26 MPE) compared to 70 PHT-tolerant controls during 2008-2017. Genotyping was performed by Taqman RT-PCR (EPHX1 337 T > C, EPHX1 416A > G and CYP2C9*3), pyrosequencing (UGT1A1*28, UGT1A1*6) and polymerase chain reaction-sequence-specific oligonucleotide probe (HLA-B). Read More

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A Genome-wide Association Study of Circulating Levels of Atorvastatin and Its Major Metabolites.

Clin Pharmacol Ther 2020 08 8;108(2):287-297. Epub 2020 Apr 8.

Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.

Atorvastatin (ATV) is frequently prescribed and generally well  tolerated, but can lead to myotoxicity, especially at higher doses. A genome-wide association study of circulating levels of ATV, 2-hydroxy (2-OH) ATV, ATV lactone (ATV L), and 2-OH ATV L was performed in 590 patients who had been hospitalized with a non-ST elevation acute coronary syndrome 1 month earlier and were on high-dose ATV (80 mg or 40 mg daily). The UGT1A locus (lead single nucleotide polymorphism, rs887829) was strongly associated with both increased 2-OH ATV/ATV (P = 7. Read More

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Comparison of Eight Technologies to Determine Genotype at the UGT1A1 (TA) Repeat Polymorphism: Potential Clinical Consequences of Genotyping Errors?

Int J Mol Sci 2020 Jan 30;21(3). Epub 2020 Jan 30.

Clinical Pharmacology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

To ensure accuracy of (rs3064744) genotyping for use in pharmacogenomics-based irinotecan dosing, we tested the concordance of several commonly used genotyping technologies. Heuristic genotype groupings and principal component analysis demonstrated concordance for Illumina sequencing, fragment analysis, and fluorescent PCR. However, Illumina sequencing and fragment analysis returned a range of fragment sizes, likely arising due to PCR "slippage". Read More

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January 2020

Influence of Uridine Diphosphate Glucuronosyltransferase Family 1 Member A1 and Solute Carrier Organic Anion Transporter Family 1 Member B1 Polymorphisms and Efavirenz on Bilirubin Disposition in Healthy Volunteers.

Drug Metab Dispos 2020 03 30;48(3):169-175. Epub 2019 Dec 30.

Department of Medicine, Division of Clinical Pharmacology (K.S.C., I.F.M., B.T.G., J.L., T.C.S., Z.D.), and Department of Medical and Molecular Genetics (E.B.M., V.M.P.), Indiana University School of Medicine, Indianapolis, Indiana

Chronic administration of efavirenz is associated with decreased serum bilirubin levels, probably through induction of We assessed the impact of efavirenz monotherapy and UGT1A1 phenotypes on total, conjugated, and unconjugated serum bilirubin levels in healthy volunteers. Healthy volunteers were enrolled into a clinical study designed to address efavirenz pharmacokinetics, drug interactions, and pharmacogenetics. Volunteers received multiple oral doses (600 mg/day for 17 days) of efavirenz. Read More

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Regorafenib plus FOLFIRI with irinotecan dose escalated according to uridine diphosphate glucuronosyltransferase 1A1genotyping in previous treated metastatic colorectal cancer patients:study protocol for a randomized controlled trial.

Trials 2019 Dec 19;20(1):751. Epub 2019 Dec 19.

Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan.

Background: Regorafenib is an oral multikinase inhibitor for metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidines, irinotecan, oxaliplatin, monoclonal antibodies targeting vascular endothelial growth factor, and monoclonal antibodies targeting epidermal growth factor receptor. A dose reduction from 160 mg to 120 mg regorafenib reduces regorafenib-associated adverse events (AEs). Dose adjustment of irinotecan in a 5-fluorouracil/leucovorin/irinotecan (FOLFIRI) regimen on the basis of an individual uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) genotype provides optimal oncological outcomes with acceptable AEs. Read More

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December 2019

Genetic associations of docetaxel-based chemotherapy-induced myelosuppression in Chinese Han population.

J Clin Pharm Ther 2020 Apr 28;45(2):354-364. Epub 2019 Nov 28.

The Fourth People's Hospital of Jinan City, Taishan Medical College, Jinan, China.

What Is Known And Objective: Myelosuppression, an adverse drug reaction (ADR), often causes medical treatment termination in cancer patients. It has been known that genetic components, such as single-nucleotide polymorphisms (SNPs), influence the risk of myelosuppression at the individual-patient level. However, due to ethnic variation in frequency of genetic polymorphisms, results reported in Caucasian patients may not be generalizable to the Chinese Han population. Read More

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Mechanistic examination of methimazole-induced hepatotoxicity in patients with Grave's disease: a metabolomic approach.

Arch Toxicol 2020 01 18;94(1):231-244. Epub 2019 Nov 18.

Department of Clinical Pharmacy, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, People's Republic of China.

Methimazole (MMI), the first-line anti-thyroid agent used in clinical practice is known to induce hepatotoxicity in patients with Grave's disease (GD), although its exact mechanism remains largely unclear. This cohort study aimed to examine the mechanism of MMI-induced hepatotoxicity using metabolomic approach. A total of 40 GD patients with MMI-induced hepatotoxicity (responders) and 80 GD patients without MMI-induced hepatotoxicity (non-responders) were included in this study and their plasma metabolomics was profiled with targeted gas chromatography-tandem mass spectrometry (GC-MS/MS). Read More

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January 2020

Pazopanib-Induced Liver Toxicity in Patients With Metastatic Renal Cell Carcinoma: Effect of UGT1A1 Polymorphism on Pazopanib Dose Reduction, Safety, and Patient Outcomes.

Clin Genitourin Cancer 2020 02 26;18(1):62-68.e2. Epub 2019 Sep 26.

Department of Oncology, Aarhus University Hospital, Aarhus, Denmark. Electronic address:

Background: Pazopanib can induce liver toxicity in patients with metastatic renal cell carcinoma (mRCC). We assessed the effect of a TA repeat polymorphism in the UGT1A1 (uridine diphosphate glucuronosyltransferase 1A1) gene encoding uridine diphosphate glucuronosyltransferase 1A1 on liver toxicity, dose reductions, and patient outcomes.

Patients And Methods: Patients with mRCC treated with first-line pazopanib developing liver toxicity underwent genotyping for the UGT1A1 polymorphism. Read More

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February 2020

Multiplex PCR and multicolor probes melting for the simultaneous detection of five UGT1A1 variants.

Anal Biochem 2019 12 21;587:113448. Epub 2019 Sep 21.

Division of Laboratory Medicine, Chiba University Hospital, 1-8-1 Inohana, Chuo-ward, Chiba-city, Chiba, 266-8677, Japan.

The multiplex PCR melting analysis method was developed for detecting the five UGT1A1 variants. Multiplexing was achieved using color probes and T. The probes for *28/*6, *27, *29, and *7 were discriminated by colors. Read More

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December 2019

A novel deletion with two pathogenic variants of UGT1A1 causing Crigler-Najjar syndrome in two unrelated Chinese.

Clin Biochem 2019 Sep 24;71:67-68. Epub 2019 Jun 24.

Institutes of Biomedical Sciences and Children's Hospital of Fudan University, Shanghai 200032, PR China. Electronic address:

Two Chinese female infants from two unrelated families were diagnosed with Crigler-Najjar syndromes-I (CNS-I) and CNS-II respectively. The CNS-I patient had Serum Total Bilirubin Concentration (STBC) peaked at 26.1 mg/dL. Read More

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September 2019

Targeted next generation sequencing as a tool for precision medicine.

BMC Med Genomics 2019 06 3;12(1):81. Epub 2019 Jun 3.

Division of Clinical Pharmacology, Department of Medicine, Western University, London Health Sciences Centre - University Hospital, 339 Windermere Road, London, ON, N6A 5A5, Canada.

Background: Targeted next-generation sequencing (NGS) enables rapid identification of common and rare genetic variation. The detection of variants contributing to therapeutic drug response or adverse effects is essential for implementation of individualized pharmacotherapy. Successful application of short-read based NGS to pharmacogenes with high sequence homology, nearby pseudogenes and complex structure has been previously shown despite anticipated technical challenges. Read More

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Interethnic Variations of UGT1A1 and UGT1A7 Polymorphisms in the Jordanian Population.

Curr Drug Metab 2019 ;20(5):399-410

Department of Biology and Biotechnology, Hashemite University, Zarqa, Jordan.

Background: Glucuronidation is one of the most important phase II metabolic pathways. It is catalyzed by a family of UDP-glucuronosyltransferase enzymes (UGTs). UGT1A1 and UGT1A7 catalyze the glucuronidation of a diverse range of medications, environmental chemicals and endogenous compounds. Read More

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December 2019

Development of the PGx-Passport: A Panel of Actionable Germline Genetic Variants for Pre-Emptive Pharmacogenetic Testing.

Clin Pharmacol Ther 2019 10 12;106(4):866-873. Epub 2019 Jun 12.

Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands.

Pre-emptive pharmacogenetics (PGx) testing of a panel of germline genetic variants represents a new model for personalized medicine. Clinical impact of PGx testing is maximized when all variant alleles for which actionable clinical guidelines are available are included in the test panel. However, no such standardized panel has been presented to date, impeding adoption, exchange, and continuity of PGx testing. Read More

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October 2019

Effects of genetic variability on rifampicin and isoniazid pharmacokinetics in South African patients with recurrent tuberculosis.

Pharmacogenomics 2019 03 15;20(4):225-240. Epub 2019 Feb 15.

Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa.

Aim: We report the prevalence and effect of genetic variability on pharmacokinetic parameters of isoniazid and rifampicin.

Materials & Methods: Genotypes for SLCO1B1, NAT2, PXR, ABCB1 and UGT1A genes were determined using a TaqMan Genotyping OpenArray™. Nonlinear mixed-effects models were used to describe drug pharmacokinetics. Read More

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Cost-effectiveness analysis of UGT1A1*6/*28 genotyping for preventing FOLFIRI-induced severe neutropenia in Chinese colorectal cancer patients.

Pharmacogenomics 2019 03 10;20(4):241-249. Epub 2019 Jan 10.

Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, PR China.

Aim: To assess the cost-effectiveness of UGT1A1*6/*28 genotyping compared with no genotyping or no dose adjustment before irinotecan administration in China.

Materials & Methods: A decision tree model was developed to evaluate costs and health outcomes represented as quality-adjusted life years gained. Model inputs for the frequency of genotypes, the probability of neutropenia under FOLFIRI chemotherapy and direct costs and utilities were obtained from published sources. Read More

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