Qualitative gene profiling: a novel tool in genomics and in pharmacogenomics that deciphers messenger RNA isoforms diversity.

Abstract:

:RNA splicing is a tightly regulated process. It is essential for gene expression and, therefore, intervenes in every biological phenomenon in mammals. RNA splicing regulation is cell type-specific in such a way that a cellular situation can be characterised by its repertoire of spliced events, the spliceome. Comparison of the splicing repertoire of two situations identifies alternative exons and introns. This regulation involves cis-acting sequences and transacting factors. Mutations, as well as modifications of signalling pathways, can alter the accuracy of splicing. Since deletion of exons or retention of introns within coding sequences modifies the corresponding proteins and functional domains of proteins are encoded by contiguous exons, identifying changes in the spliceome pinpoints functional domains, which are specifically regulated at the level of RNA splicing. We have developed a new method of gene profiling, qualitative gene profiling, that allows the comparative study of the repertoires of spliced events that characterise distinct physiopathological situations. We present in this review the different uses of this new genomic technique that can help each step of the R&D process in the pharmaceutical industry, and that represents a short cut towards functional genomics and pharmacogenomics.

journal_name

Pharmacogenomics

journal_title

Pharmacogenomics

authors

Schweighoffer F,Ait-Ikhlef A,Resink AL,Brinkman B,Melle-Milovanovic D,Laurent-Puig P,Kearsey J,Bracco L

doi

10.1517/14622416.1.2.187

keywords:

subject

Has Abstract

pub_date

2000-05-01 00:00:00

pages

187-97

issue

2

eissn

1462-2416

issn

1744-8042

journal_volume

1

pub_type

杂志文章,评审
  • Genome-wide response to antihypertensive medication using home blood pressure measurements: a pilot study nested within the HOMED-BP study.

    abstract:BACKGROUND:Patients with mild-to-moderate essential hypertension in the HOMED-BP trial were randomly allocated to first-line treatment with a calcium channel blocker (CCB), angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB). METHODS:We recruited 265 (93 for CCB, 71 for ACEI and 101...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章

    doi:10.2217/pgs.13.161

    authors: Kamide K,Asayama K,Katsuya T,Ohkubo T,Hirose T,Inoue R,Metoki H,Kikuya M,Obara T,Hanada H,Thijs L,Kuznetsova T,Noguchi Y,Sugimoto K,Ohishi M,Morimoto S,Nakahashi T,Takiuchi S,Ishimitsu T,Tsuchihashi T,Soma M,Hig

    更新日期:2013-11-01 00:00:00

  • Conference Scene: Systems biology and personalized health science and translation.

    abstract::After a 1-day advanced course on systems biology, the main themes of this 3-day colloquium were developed: from systems biology to systems medicine with special applications to cancer; pharmacogenomics in drug discovery and clinical application; and epigenomics and genome-wide association studies in cardiovascular dis...

    journal_title:Pharmacogenomics

    pub_type:

    doi:10.2217/pgs.13.201

    authors: Siest G,Ndiaye NC,El Shamieh S,Shahabi P,Stathopoulou M,Saleh AS,Godjo T,Albertini L,Visvikis-Siest S

    更新日期:2013-12-01 00:00:00

  • Screening CYP3A single nucleotide polymorphisms in a Han Chinese population with a genotyping chip.

    abstract::Human cytochrome P450 (CYP)3A is a major P450 enzyme found in the liver and gastrointestinal tract. It plays an important role in the metabolism of a wide variety of drugs, some endogenous steroids and harmful environmental contaminants. It has been shown that CYP3A alleles encoding enzymes with little or no activity ...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章

    doi:10.2217/14622416.6.7.731

    authors: Liu CH,Peck K,Huang JD,Lin MS,Wang CH,Hsu WP,Wang HW,Lee HL,Lai ML

    更新日期:2005-10-01 00:00:00

  • Cytidine deaminase genetic variants influence RNA expression and cytarabine cytotoxicity in acute myeloid leukemia.

    abstract:AIM:Cytidine deaminase (CDA) irreversibly deaminates cytarabine (Ara-C), a key component of acute myeloid leukemia (AML) induction and consolidation therapy. CDA overexpression results in Ara-C resistance, while decreased expression is associated with toxicity. We evaluated factors influencing variation in CDA mRNA exp...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章

    doi:10.2217/pgs.11.149

    authors: Abraham A,Varatharajan S,Abbas S,Zhang W,Shaji RV,Ahmed R,Abraham A,George B,Srivastava A,Chandy M,Mathews V,Balasubramanian P

    更新日期:2012-02-01 00:00:00

  • Voriconazole and atazanavir: a CYP2C19-dependent manageable drug-drug interaction.

    abstract:AIM:To investigate the pharmacokinetics of voriconazole when administered to HIV-positive patients receiving treatment with atazanavir-containing therapies according to CYP2C19 genotype. MATERIALS & METHODS:We describe four HIV-positive patients with pulmonary aspergillosis treated with voriconazole and atazanavir-bas...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章

    doi:10.2217/pgs.14.92

    authors: Calcagno A,Baietto L,Pagani N,Simiele M,Audagnotto S,D'Avolio A,De Rosa FG,Di Perri G,Bonora S

    更新日期:2014-07-01 00:00:00

  • Drug-induced liver injury: insights from genetic studies.

    abstract::Drug-induced liver injury (DILI) is an increasing health problem and a challenge for physicians, regulatory bodies and the pharmaceutical industry, not only because of its potential severity and elusive pathogenesis but also because it is often inaccurately diagnosed, commonly missed entirely and more often not report...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章,评审

    doi:10.2217/pgs.09.111

    authors: Andrade RJ,Robles M,Ulzurrun E,Lucena MI

    更新日期:2009-09-01 00:00:00

  • Challenges for molecular profiling of chronic fatigue syndrome.

    abstract::Chronic fatigue syndrome (CFS) is prevalent, disabling and costly. Despite extensive literature describing the epidemiology and clinical aspects of CFS, it has been recalcitrant to diagnostic biomarker discovery and therapeutic intervention. This is due to the fact that CFS is a complex illness defined by self-reporte...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章,评审

    doi:10.2217/14622416.7.2.211

    authors: Vernon SD,Whistler T,Aslakson E,Rajeevan M,Reeves WC

    更新日期:2006-03-01 00:00:00

  • Pharmacogenetics and the treatment of HIV-/HCV-coinfected patients.

    abstract::This review will summarize the role of pharmacogenetics in the natural history of hepatitis C, particularly in patients with HIV/HCV and will take the perspective of pharmacogenetics and its influence on the response to antiviral therapy and the susceptibility to develop adverse effects. This review will also devote a...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章,评审

    doi:10.2217/pgs-2018-0046

    authors: Frias M,Rivero-Juárez A,López-López P,Rivero A

    更新日期:2018-08-01 00:00:00

  • The application of CD antigen proteomics to pharmacogenomics.

    abstract::The advent of multiplexing technologies has raised the possibility that disease states can be defined using discrete genomic and proteomic patterns or signatures. However, this emerging area has been limited by the 'content problem', arising from the uncertainty of which molecules to focus on. The human cluster of dif...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章,评审

    doi:10.2217/14622416.7.5.759

    authors: Woolfson A,Ellmark P,Chrisp JS,A Scott M,Christopherson RI

    更新日期:2006-07-01 00:00:00

  • Carvedilol pharmacokinetics and pharmacodynamics in relation to CYP2D6 and ADRB pharmacogenetics.

    abstract:AIMS:Carvedilol is an effective treatment in hypertension and chronic heart failure. The medical impact of polymorphisms in CYP2D6 and in the β-adrenergic receptors ADRB1 and ADRB2 on the pharmacokinetics and pharmacodynamics of carvedilol is controversial. METHODS:After carvedilol 25 mg was administered to 110 volunt...

    journal_title:Pharmacogenomics

    pub_type: 临床试验,杂志文章

    doi:10.2217/pgs.11.20

    authors: Sehrt D,Meineke I,Tzvetkov M,Gültepe S,Brockmöller J

    更新日期:2011-06-01 00:00:00

  • DNA methylation biomarkers of cancer: moving toward clinical application.

    abstract::While different markers for cancer diagnosis have been known for at least a decade, the systematic search for biomarkers emerged only several years ago. In this article, I will concentrate on DNA methylation as a dynamic and robust platform for the development of cancer-specific biomarkers. Simultaneous analysis of a ...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章,评审

    doi:10.1517/14622416.5.6.699

    authors: Levenson VV

    更新日期:2004-09-01 00:00:00

  • Personalized sequencing and the future of medicine: discovery, diagnosis and defeat of disease.

    abstract::The potential for personalized sequencing to individually optimize medical treatment in diseases such as cancer and for pharmacogenomic application is just beginning to be realized, and the utility of sequencing healthy individuals for managing health is also being explored. The data produced requires additional advan...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章

    doi:10.2217/pgs.14.117

    authors: Esplin ED,Oei L,Snyder MP

    更新日期:2014-11-01 00:00:00

  • 677C>T and 1298A>C MTHFR polymorphisms affect methotrexate treatment outcome in rheumatoid arthritis.

    abstract:INTRODUCTION:Methotrexate (MTX), widely used in the treatment of rheumatoid arthritis (RA), inhibits dihydrofolate reductase and folate-dependent enzymes. Methylenetetrahydrofolate reductase (MTHFR) is involved in folate metabolism and has been shown to be polymorphic, affecting the enzyme activity. METHODS:To examine...

    journal_title:Pharmacogenomics

    pub_type: 临床试验,杂志文章

    doi:10.2217/14622416.8.11.1551

    authors: Kurzawski M,Pawlik A,Safranow K,Herczynska M,Drozdzik M

    更新日期:2007-11-01 00:00:00

  • Gene expression profile analysis: an emerging approach to investigate mechanisms of genotoxicity.

    abstract::The response to stress triggers transcriptional activation of genes involved in cell survival and/or cell death. Thus, the monitoring of gene expression levels in large gene sets or whole genomes in response to various agents (toxicogenomics) has been proposed as a tool for investigating mechanisms of toxicity. Althou...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章,评审

    doi:10.1517/14622416.6.4.419

    authors: Aubrecht J,Caba E

    更新日期:2005-06-01 00:00:00

  • The significance of genetic polymorphisms in modulating the response to lipid-lowering drugs.

    abstract::The response to lipid-lowering drugs is modified by a number of factors like age, gender, concomitant disease and genetic determinants. Even within homogenous groups of patients, individual responses vary greatly. Until now, no clinical or biochemical parameter exists which predicts whether a subject will respond well...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章,评审

    doi:10.1517/14622416.2.2.107

    authors: Hoffmann MM,Winkelmann BR,Wieland H,März W

    更新日期:2001-05-01 00:00:00

  • Association of the HLA-B alleles with carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis in the Javanese and Sundanese population of Indonesia: the important role of the HLA-B75 serotype.

    abstract::Carbamazepine (CBZ) is a common cause of life-threatening cutaneous adverse drug reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Previous studies have reported a strong association between the HLA genotype and CBZ-induced SJS/TEN. We investigated the association between the HLA g...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章

    doi:10.2217/pgs-2017-0103

    authors: Yuliwulandari R,Kristin E,Prayuni K,Sachrowardi Q,Suyatna FD,Menaldi SL,Wichukchinda N,Mahasirimongkol S,Cavallari LH

    更新日期:2017-12-01 00:00:00

  • Association between CYP2D6 genotypes and the clinical outcomes of adjuvant tamoxifen for breast cancer: a meta-analysis.

    abstract:AIM:Tamoxifen is one of the most commonly used endocrine therapeutic agents for breast cancer. Although many studies have examined whether the treatment outcomes of tamoxifen for breast cancer differ according to CYP2D6 genotype, the study results have been inconsistent, and the role of CYP2D6 in the prediction of pati...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章,meta分析

    doi:10.2217/pgs.13.221

    authors: Jung JA,Lim HS

    更新日期:2014-01-01 00:00:00

  • Economic evaluation of pharmacogenomic-guided warfarin treatment for elderly Croatian atrial fibrillation patients with ischemic stroke.

    abstract:BACKGROUND & METHODS:Economic evaluation in genomic medicine is an emerging discipline to assess the cost-effectiveness of genome-guided treatment. Here, we developed a pharmaco-economic model to assess whether pharmacogenomic (PGx)-guided warfarin treatment of elderly ischemic stroke patients with atrial fibrillation ...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章,随机对照试验

    doi:10.2217/pgs.14.167

    authors: Mitropoulou C,Fragoulakis V,Bozina N,Vozikis A,Supe S,Bozina T,Poljakovic Z,van Schaik RH,Patrinos GP

    更新日期:2015-01-01 00:00:00

  • Building bridges to the future of medicine: recommendations for boosting development of novel and companion diagnostics.

    abstract::Evaluating the prospects for 'personalized healthcare' has become topical at the 10-year anniversary of the first results from the Human Genome Project. The coincidence of this milestone with a period of global financial difficulty is unfortunate, but industry has signaled its willingness to invest in this new medical...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章

    doi:10.2217/pgs.12.143

    authors: Creeden J

    更新日期:2012-11-01 00:00:00

  • The pharmacogenetics of NAT: structural aspects.

    abstract::Arylamine N-acetyltransferases (NATs) catalyze the transfer of an acetyl group from acetyl-CoA to arylhydrazines and to arylamine drugs and carcinogens or to their N-hydroxylated metabolites. NAT plays an important role in detoxification and metabolic activation of xenobiotics and was first identified as the enzyme re...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章,评审

    doi:10.1517/14622416.3.1.19

    authors: Pompeo F,Brooke E,Kawamura A,Mushtaq A,Sim E

    更新日期:2002-01-01 00:00:00

  • Fibrate pharmacogenomics: expanding past the genome.

    abstract::Fibrates are a medication class prescribed for decades as 'broad-spectrum' lipid-modifying agents used to lower blood triglyceride levels and raise high-density lipoprotein cholesterol levels. Such lipid changes are associated with a decrease in cardiovascular disease, and fibrates are commonly used to reduce risk of ...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章

    doi:10.2217/pgs-2019-0140

    authors: House JS,Motsinger-Reif AA

    更新日期:2020-03-01 00:00:00

  • The effect of ABCB1 genetic variants on chemotherapy response in HIV and cancer treatment.

    abstract::Despite their clearly distinct pathophysiologies, HIV and cancer are diseases whose response to chemotherapy treatment varies substantially amongst patients, in particular for those with prior drug exposure. This has been attributed, in part, to elevated expression of the ABCB1 drug transporter in some patients, which...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章,评审

    doi:10.2217/pgs.11.84

    authors: Reed K,Parissenti AM

    更新日期:2011-10-01 00:00:00

  • Evaluation of a shared pharmacogenomics curriculum for pharmacy students.

    abstract:AIM:This national dissemination study evaluated pharmacy students' self-reported overall ability, self-efficacy and attitudes toward applying pharmacogenomics and perceptions of Pharmacogenomics Education Program, a shared pharmacogenomics curriculum. PATIENTS & METHODS:Following a series of train-the-trainer programs...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章

    doi:10.2217/pgs.14.181

    authors: Lee KC,Hudmon KS,Ma JD,Kuo GM

    更新日期:2015-01-01 00:00:00

  • Pyrosequencing-based screening for genetic polymorphisms in cytochrome P450 2B6 of potential clinical relevance.

    abstract:OBJECTIVES:Three exonic single nucleotide polymorphisms (SNPs) in the cytochrome P450 2B6 (CYP2B6) gene, 516G>T, 785A>G and 1459C>T, have been described to be associated with functional changes in the CYP2B6 catalytic activity or protein expression. They are therefore of potential clinical importance for drug efficacy ...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章

    doi:10.2217/14622416.7.7.995

    authors: Rohrbacher M,Kirchhof A,Geisslinger G,Lötsch J

    更新日期:2006-10-01 00:00:00

  • History repeats itself: the family medication history and pharmacogenomics.

    abstract::Related to many drug gene-product interactions, application of pharmacogenomics can lead to improved medication efficacy while decreasing or avoiding adverse drug reactions. However, utilizing pharmacogenomics without other information does not allow for optimal medication therapy. Currently, there is a lack of docume...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章

    doi:10.2217/pgs-2015-0015

    authors: Smith TR,Kearney E,Hulick PJ,Kisor DF

    更新日期:2016-05-01 00:00:00

  • Pharmacokinetic and CYP3A5 pharmacogenetic differences between once- and twice-daily tacrolimus from the first dosing day to 1 year after renal transplantation.

    abstract:UNLABELLED:Aim & patients & methods: This study investigated 24-h pharmacokinetic and CYP3A5 pharmacogenetic differences between once-daily tacrolimus (Tac-q.d.) versus twice-daily tacrolimus (Tac-b.i.d.) pretransplantation and at 1 month and 1 year post-transplantaion. RESULTS:The dose-adjusted trough level (Cmin) an...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章

    doi:10.2217/pgs.14.98

    authors: Satoh S,Niioka T,Kagaya H,Numakura K,Inoue T,Saito M,Komine N,Narita S,Tsuchiya N,Habuchi T,Miura M

    更新日期:2014-08-01 00:00:00

  • The role of genomics in the discovery of novel targets for antibiotic therapy.

    abstract::The emergence of antibiotic resistance and multi-drug resistance in bacterial pathogens underscores the need for the development of novel classes of antibiotics. The availability of complete genome sequence data from many important human pathogens provides a wealth of fundamental information. This allows us to define ...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章,评审

    doi:10.1517/14622416.3.3.315

    authors: Ji Y

    更新日期:2002-05-01 00:00:00

  • Resequencing CYP2D6 gene in Indian population: CYP2D6*41 identified as the major reduced function allele.

    abstract::Aim: The CYP2D6 gene is highly polymorphic and harbors population specific alleles that define its predominant metabolizer phenotype. This study aimed to identify polymorphisms in Indian population owing to scarcity of CYP2D6 data in this population. Materials & methods: The CYP2D6 gene was resequenced in 105 south In...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章

    doi:10.2217/pgs-2019-0049

    authors: Manoharan A,Shewade DG,Ravindranath PA,Rajkumar RP,Ramprasad VL,Adithan S,Damodaran SE

    更新日期:2019-07-01 00:00:00

  • Association of CYP2A6 polymorphisms with S-1 plus docetaxel therapy outcomes in metastatic gastric cancer.

    abstract:AIMS:S-1, an oral fluoropyrimidine, contains tegafur, which is converted to 5-fluorouracil mainly by CYP2A6. We evaluated the association between CYP2A6 polymorphisms and treatment outcome in metastatic gastric cancer patients treated with S-1 plus docetaxel. MATERIALS & METHODS:Chemonaive patients received S-1 40 mg/...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章

    doi:10.2217/pgs.09.48

    authors: Kong SY,Lim HS,Nam BH,Kook MC,Kim YW,Ryu KW,Lee JH,Choi IJ,Lee JS,Park YI,Kim NK,Park SR

    更新日期:2009-07-01 00:00:00

  • Integrating pharmacogenomics into drug development.

    abstract::The first observations of inherited differences in drug effects in the 1950s led to the recognition of a genetic basis for drug response. With the development of genetics and molecular biology, it became clear that certain drug responses could be associated with specific genetic variations or polymorphisms. There are ...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章,评审

    doi:10.1517/14622416.3.4.453

    authors: Ferentz AE

    更新日期:2002-07-01 00:00:00