Search results for "CYP3A5"

showing 10 items of 15 documents

2017

Abstract Background Results on the association between prenatal exposure to methylmercury (MeHg) and child neuropsychological development are heterogeneous. Underlying genetic differences across study populations could contribute to this varied response to MeHg. Studies in Drosophila have identified the cytochrome p 450 3A (CYP3A) family as candidate MeHg susceptibility genes. Objectives We evaluated whether genetic variation in CYP3A genes influences the association between prenatal exposure to MeHg and child neuropsychological development. Methods The study population included 2639 children from three birth cohort studies: two subcohorts in Seychelles (SCDS) (n = 1160, 20 and 30 months of…

0301 basic medicine2. Zero hungerGeneticsPhysiology010501 environmental sciencesBiology01 natural sciencesBayley Scales of Infant Development03 medical and health scienceschemistry.chemical_compound030104 developmental biologychemistryCord bloodGenetic variationPopulation studyAlleleCYP3A5MethylmercuryCYP3A70105 earth and related environmental sciencesGeneral Environmental ScienceEnvironment International
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Unusual high dose of tacrolimus in liver transplant patient, a case report.

2012

Case We describe the case of a liver transplant patient who had great difficulty in reaching the desired trough blood levels despite the use of high dose tacrolimus. The patient was homozygous for the CYP3A5*3 allele. However, the respective donor carried the wild-type CYP3A5*1/*1 genotype. Regarding ABCB1 SNPs at exon 21 and 26, the patient showed the 2677GT and 3435CC genotypes. For the corresponding donor we observed the 2677GG and 3435CC wild-type genotypes. One, two and three weeks after transplantation the patient received daily 0.219, 0.287 and 0.273 mg/kg of tacrolimus, respectively. However, the corresponding tacrolimus trough blood levels were of 4.6, 5.6 and 6.1 ng/mL. The tacrol…

AdultGraft RejectionMalemedicine.medical_specialtyATP Binding Cassette Transporter Subfamily BPharmaceutical SciencePharmacyToxicologyGastroenterologyPolymorphism Single NucleotideTacrolimusInternal medicineGenotypemedicineCytochrome P-450 CYP3AHumansPharmacology (medical)ATP Binding Cassette Transporter Subfamily B Member 1CYP3A5GenotypingPharmacologyKidneybusiness.industryGraft SurvivalHomozygoteLiver transplant patient tacrolimus dose CYP3A5 ABCB1 SNPMiddle AgedTacrolimusTissue DonorsSurgeryLiver TransplantationTransplantationsurgical procedures operativemedicine.anatomical_structurePhenotypeTreatment OutcomePharmacogeneticsToxicitySettore BIO/14 - FarmacologiaDrug MonitoringbusinessPharmacogeneticsImmunosuppressive AgentsInternational journal of clinical pharmacy
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Influence of CYP3A5 and ABCB1 gene polymorphisms and other factors on tacrolimus dosing in Caucasian liver and kidney transplant patients

2011

Tacrolimus is a substrate of cytochrome P4503A (CYP3A) enzymes as well as of the drug transporter ABCB1. We have investigated the possible influence of CYP3A5 and ABCB1 single nucleotide polymorphisms (SNPs) and other factors (e.g. albumin, hematocrit and steroids) on tacrolimus blood levels achieved in a population of Caucasian liver (n=51) and kidney (n=50) transplant recipients. At 1, 3 and 6 months after transplantation, tacrolimus doses (mg/kg/day) and trough blood levels (C0) were recorded and the weight-adjusted tacrolimus dosage (mg/kg/day) was calculated. Polymerase chain reaction followed by restriction fragment length polymorphism analysis was used for genotyping CYP3A5*1 and *3 …

AdultMalemedicine.medical_specialtyATP Binding Cassette Transporter Subfamily BGenotypemedicine.medical_treatmentDNA Mutational AnalysisPopulationSingle-nucleotide polymorphismLiver transplantationBiologyKidneyPolymorphism Single NucleotideGastroenterologyBiomarkers PharmacologicalTacrolimusWhite PeopleGene FrequencyInternal medicineGeneticsmedicineCytochrome P-450 CYP3AHumansDrug Dosage CalculationsATP Binding Cassette Transporter Subfamily B Member 1educationAllele frequencyAllelesKidney transplantationAgededucation.field_of_studyKidney metabolismGeneral MedicineMiddle Agedmedicine.diseaseKidney TransplantationTacrolimusLiver TransplantationTransplantationsurgical procedures operativeItalyLiverImmunologySettore BIO/14 - FarmacologiaPharmacogenetics CYP3A5 ABCB1 TacrolimusTransplant patientsFemaleImmunosuppressive AgentsPolymorphism Restriction Fragment LengthInternational Journal of Molecular Medicine
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Meta-analysis and systematic review of the effect of the donor and recipient CYP3A5 6986A>G genotype on tacrolimus dose requirements in liver tran…

2013

Objective A meta-analysis was carried out of publishedstudies on the effect of the CYP3A5 6986A>Gpolymorphism in liver donors and transplant recipientson tacrolimus pharmacokinetics.Methods Cohort studies that evaluated the relationshipbetween the CYP3A5 polymorphism in liver donors andtransplant recipients and tacrolimus, trough bloodconcentration normalized for the daily dose (C) perkilogram body weight (D) (C/D, ng/ml/mg/kg/day) up to1 year after transplantation, were included. Data were notrestricted by patient age or the language or journal ofpublication. A literature search was conducted using theCochrane Library, MEDLINE, EMBASE, and grey literature,and articles published up to 24 Ap…

Adultmedicine.medical_specialtyAdolescentGenotypemedicine.medical_treatmentLiver transplantationPolymorphism Single NucleotideGastroenterologyTacrolimusYoung AdultInternal medicineGenotypeLiving DonorsGeneticsCytochrome P-450 CYP3AHumansMedicineGeneral Pharmacology Toxicology and PharmaceuticsCYP3A5Molecular BiologyGenetics (clinical)AgedAged 80 and overTransplantationbusiness.industryGenetic VariationMiddle AgedTacrolimusLiver TransplantationTransplantationMeta-analysisImmunologyMolecular MedicinebusinessImmunosuppressive AgentsPharmacogeneticsCohort studyPharmacogenetics and Genomics
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Pharmacogenetic considerations for optimizing tacrolimus dosing in liver and kidney transplant patients

2013

The introduction of tacrolimus in clinical practice has improved patient survival after organ transplant. However, despite the long use of tacrolimus in clinical practice, the best way to use this agent is still a matter of intense debate. The start of the genomic era has generated new research areas, such as pharmacogenetics, which studies the variability of drug response in relation to the genetic factors involved in the processes responsible for the pharmacokinetics and/or the action mechanism of a drug in the body. This variability seems to be correlated with the presence of genetic polymorphisms. Genotyping is an attractive option especially for the initiation of the dosing of tacrolim…

Graft Rejectionmedicine.medical_specialtyCYP3A5ATP Binding Cassette Transporter Subfamily BCYP3A4Genotypemedicine.medical_treatmentPharmacologyLiver transplantationBioinformaticsOrgan transplantationTacrolimusCalcineurin inhibitorMedicineCytochrome P-450 CYP3AHumansDrug Dosage CalculationsDosingATP Binding Cassette Transporter Subfamily B Member 1Topic HighlightKidney transplantLiver transplantKidney transplantationBiotransformationPolymorphism Geneticbusiness.industryPharmacogeneticGraft SurvivalGastroenterologyABCB1General Medicinemedicine.diseaseKidney TransplantationTacrolimusLiver TransplantationSingle nucleotide polymorphismTransplantationsurgical procedures operativePhenotypeTreatment OutcomePharmacogeneticsTacrolimuSettore BIO/14 - FarmacologiaPersonalized medicinebusinessPharmacogeneticsImmunosuppressive Agents
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Effect of CYP3A5*3 on kidney transplant recipients treated with tacrolimus: a systematic review and meta-analysis of observational studies

2014

The highly variable pharmacokinetics of tacrolimus can hamper the optimal management of kidney transplant patients. This variability has been attributed to the genetic polymorphism of CYP3A5 6986A>G, but the evidence is not clear. We conducted a meta-analysis of studies evaluating the effect of CYP3A5 polymorphism on kidney transplant recipients with tacrolimus plasma concentration divided by daily dose per body weight (C/D) and clinical outcomes. We searched in MEDLINE and EMBASE. We found evidence suggesting a significantly lower C/D among CYP3A5*1 allele carriers compared with carriers of the CYP3A5*3/*3 genotype at weeks 1 and 2, and months 1, 3, 6 and 12. We demonstrated that the expre…

Graft Rejectionmedicine.medical_specialtyPharmacologyGastroenterologyKidney transplantTacrolimusPharmacokineticsInternal medicineGenotypeGeneticsmedicineCytochrome P-450 CYP3AHumansAlleleCYP3A5Pharmacologybusiness.industryKidney TransplantationTransplant RecipientsTacrolimusObservational Studies as Topicsurgical procedures operativeMeta-analysisMolecular MedicineObservational studybusinessImmunosuppressive Agents
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Genetic signature consistent with selection against the CYP3A4*1B allele in non-African populations.

2005

Cytochrome P450 3A enzymes (CYP3A) play a major role in the metabolism of steroid hormones, drugs and other chemicals, including many carcinogens. The individually variable CYP3A expression, which remains mostly unexplained, has been suggested to affect clinical phenotypes. We investigated the CYP3A locus in five ethnic groups. The degree of linkage disequilibrium (LD) differed among ethnic groups, but the most common alleles of the conserved LD regions were remarkably similar. Non-African haplotypes are few; for example, only four haplotypes account for 80% of common European Caucasian alleles. Large LD blocks of high frequencies were suggestive of selection. Accordingly, European Caucasia…

Linkage disequilibriumPopulationBlack PeopleSingle-nucleotide polymorphismLocus (genetics)BiologyLinkage DisequilibriumWhite PeopleAsian PeopleCytochrome P-450 Enzyme SystemGeneticsCytochrome P-450 CYP3AHumansGeneral Pharmacology Toxicology and PharmaceuticsAlleleSelection GeneticeducationCYP3A5Molecular BiologyGenetics (clinical)AllelesGeneticseducation.field_of_studyHaplotypeGenetic VariationHaplotypesLiverMolecular MedicinePharmacogeneticsPharmacogenetics and genomics
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Pharmacogenetic Study of ABCB1 and CYP3A5 Genes During the First Year Following Heart Transplantation Regarding Tacrolimus or Cyclosporine Levels

2011

Pharmacogenetics explains part of the interindividual variability in drug responses. Many published works about the effects of single nucleotide polymorphisms (SNPs) on immunosuppressive drug blood levels present contradictory results. We evaluated the SNPs in ABCB1 (glycoprotein P) and CYP3A5 (metabolic enzyme) genes, seeking correlate them with tacrolimus or cyclosporine levels during the first year after heart transplantation. One blood sample was obtained from each of 41 patients: 26 treated with cyclosporine and 15 with tacrolimus. We characterize the SNPs rs1045642, 1128503, 2032582, 2235013, 2235033, 2229109, 3213619, 9282564 in ABCB1 and rs10264272, 776746 in CYP3A5 genes using the …

Linkage disequilibriummedicine.medical_specialtyATP Binding Cassette Transporter Subfamily BGenotypemedicine.medical_treatmentSingle-nucleotide polymorphismBiologyPharmacologyPolymorphism Single NucleotideGastroenterologyLinkage DisequilibriumTacrolimusGene FrequencyInternal medicineGenotypemedicineCytochrome P-450 CYP3AHumansDrug Dosage CalculationsATP Binding Cassette Transporter Subfamily B Member 1CYP3A5Heart transplantationTransplantationTacrolimusPhenotypeImmunosuppressive drugPharmacogeneticsSpainCyclosporineHeart TransplantationSurgeryDrug MonitoringImmunosuppressive AgentsPharmacogeneticsTransplantation Proceedings
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The effect of CYP3A5 and ABCB1 single nucleotide polymorphisms on tacrolimus dose requirements in Caucasian liver transplant patients

2008

Background: Tacrolimus is a substrate of cytochrome P-450 (CYP) 3A enzyme and of the drug transporter ABCBl. We have investigated the effects of possible relevant CYP3A5 and ABCBl single nucleotide polymorphisms (SNPs) present in both donors and recipients on tacrolimus blood levels achieved in a population of 32 Caucasian liver transplant patients. Material/Methods: At 1, 3 and 6 months after transplantation, tacrolimus doses (mg/kg/day) and trough blood levels (C0) were determined. Polymerase chain reaction followed by restriction fragment length polymorphism analysis was used for gen-otyping CYP3A5*3 [6986A>G] as well as ABCBl at exons 21 [2677G>T] and 26 [3435C>T]. Results:87.5…

MaleCYP3A5ATP Binding Cassette Transporter Subfamily BGenotypeHomozygoteABCB1Polymorphism Single NucleotideTacrolimusWhite PeopleLiver Transplantationliver transplantPharmacogeneticssingle nucleotide polymorphismTacrolimuSettore BIO/14 - FarmacologiaCytochrome P-450 CYP3AHumansFemaleATP Binding Cassette Transporter Subfamily B Member 1Tacrolimus; single nucleotide polymorphisms; CYP3A5; ABCB1; liver transplantImmunosuppressive Agents
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Pregnane X receptor and yin yang 1 contribute to the differential tissue expression and induction of CYP3A5 and CYP3A4.

2012

The hepato-intestinal induction of the detoxifying enzymes CYP3A4 and CYP3A5 by the xenosensing pregnane X receptor (PXR) constitutes a key adaptive response to oral drugs and dietary xenobiotics. In contrast to CYP3A4, CYP3A5 is additionally expressed in several, mostly steroidogenic organs, which creates potential for induction-driven disturbances of the steroid homeostasis. Using cell lines and mice transgenic for a CYP3A5 promoter we demonstrate that the CYP3A5 expression in these organs is non-inducible and independent from PXR. Instead, it is enabled by the loss of a suppressing yin yang 1 (YY1)-binding site from the CYP3A5 promoter which occurred in haplorrhine primates. This YY1 sit…

MaleReceptors SteroidDrugs and DevicesMolecular Sequence Datalcsh:MedicineSequence HomologyMice TransgenicBiologyModels BiologicalMolecular GeneticsMiceDogsGene expressionMolecular Cell BiologyGeneticsAnimalsCytochrome P-450 CYP3AHumansTissue DistributionEvolutionary SystematicsPharmacokineticsEnzyme inducerBinding sitelcsh:ScienceBiologyCYP3A5 GeneCells CulturedPhylogenyYY1 Transcription FactorPregnane X receptorEvolutionary BiologyMultidisciplinaryCYP3A4Base SequenceYY1lcsh:RPregnane X ReceptorComputational BiologyPromoterMolecular biologyOrganismal EvolutionMice Inbred C57BLNephrologyEnzyme Inductionbiology.proteinMedicinelcsh:QFemaleResearch ArticlePloS one
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