2013
Toll-like receptor genetic variants are associated with Gram-negative infections in VLBW infants
Sampath V, Mulrooney N, Garland J, He J, Patel A, Cohen J, Simpson P, Hines R. Toll-like receptor genetic variants are associated with Gram-negative infections in VLBW infants. Journal Of Perinatology 2013, 33: 772-777. PMID: 23867959, PMCID: PMC4465440, DOI: 10.1038/jp.2013.80.Peer-Reviewed Original ResearchMeSH KeywordsBlack or African AmericanFemaleGenetic Predisposition to DiseaseGenetic VariationGram-Negative Bacterial InfectionsHumansImmunity, InnateInfant, NewbornInfant, PrematureInfant, Premature, DiseasesInfant, Very Low Birth WeightInterleukin-1 Receptor-Associated KinasesLeukocyte CountLogistic ModelsMalePolymorphism, Single NucleotideRisk FactorsToll-Like Receptor 4Toll-Like Receptor 5Toll-Like ReceptorsWhite PeopleConceptsWhite blood cellsToll-like receptorsGram-negative infectionsVLBW infantsBacterial infectionsSingle nucleotide polymorphismsLow birth weight infantsTLR single nucleotide polymorphismsBirth weight infantsElevated WBC countGenetic variantsWeight infantsMulticenter studyTLR4 variantsWBC countFemale infantImmune responseInfantsInfection rateInfectionAlters susceptibilityBlood cellsRegression modelsConfoundersCohort
2012
Developmental expression of drug metabolizing enzymes: Impact on disposition in neonates and young children
Hines R. Developmental expression of drug metabolizing enzymes: Impact on disposition in neonates and young children. International Journal Of Pharmaceutics 2012, 452: 3-7. PMID: 22766445, DOI: 10.1016/j.ijpharm.2012.05.079.Peer-Reviewed Original ResearchMeSH KeywordsChildChild DevelopmentGenetic VariationHumansInfant, NewbornLiverPharmaceutical PreparationsConceptsPerinatal changesDrug dispositionPediatric drug safetyYoung childrenDrug metabolizing enzymesAge-dependent changesSignificant interindividual variationAdverse eventsPharmacogenetic factorsHepatic drugFunctional genetic variantsDrug safetyDrug efficacyMetabolizing enzymesPharmacokinetic modelInterindividual variationEnzyme ontogenyDrugsEnzyme expressionChildrenClass 3Genetic variantsMajor determinantClass 1Current knowledge
2011
A TLR5 (g.1174C > T) variant that encodes a stop codon (R392X) is associated with bronchopulmonary dysplasia
Sampath V, Garland J, Le M, Patel A, Konduri G, Cohen J, Simpson P, Hines R. A TLR5 (g.1174C > T) variant that encodes a stop codon (R392X) is associated with bronchopulmonary dysplasia. Pediatric Pulmonology 2011, 47: 460-468. PMID: 22058078, DOI: 10.1002/ppul.21568.Peer-Reviewed Original ResearchMeSH KeywordsBronchopulmonary DysplasiaCodon, TerminatorCohort StudiesFemaleGenetic Predisposition to DiseaseGenetic VariationHeterozygoteHumansIncidenceInfant, NewbornInfant, PrematureInfant, Very Low Birth WeightInterleukin-1 Receptor-Associated KinasesMalePilot ProjectsPolymorphism, Single NucleotideProspective StudiesSeverity of Illness IndexToll-Like Receptor 5ConceptsSevere BPDExact testLow birth weight infantsVariant allelesToll-like receptor (TLR) familyBronchopulmonary dysplasia susceptibilityBirth weight infantsPathway single nucleotide polymorphismsTLR pathway genesMulti-center studyFisher's exact testSusceptibility/severityBPD outcomesEpidemiological confoundersBronchopulmonary dysplasiaMultiplexed single-base extension assayPreterm infantsBPD pathogenesisPremature infantsPulmonary homeostasisLower incidencePathogen recognitionBlood samplesClinical informationCurrent evidence
2008
Novel CYP2C9 Promoter Variants and Assessment of Their Impact on Gene Expression
Kramer M, Rettie A, Rieder M, Cabacungan E, Hines R. Novel CYP2C9 Promoter Variants and Assessment of Their Impact on Gene Expression. Molecular Pharmacology 2008, 73: 1751-1760. PMID: 18310303, PMCID: PMC2413059, DOI: 10.1124/mol.107.044149.Peer-Reviewed Original Research
2007
Identification and Functional Analysis of a Novel Human CYP2E1 Far Upstream Enhancer
Shadley J, Divakaran K, Munson K, Hines R, Douglas K, McCarver D. Identification and Functional Analysis of a Novel Human CYP2E1 Far Upstream Enhancer. Molecular Pharmacology 2007, 71: 1630-1639. PMID: 17353354, DOI: 10.1124/mol.106.031302.Peer-Reviewed Original ResearchMeSH KeywordsBase SequenceBinding SitesCells, CulturedCytochrome P-450 CYP2E1Enhancer Elements, GeneticGATA4 Transcription FactorGene Expression Regulation, EnzymologicGenetic VariationHepatocytesHumansMolecular Sequence DataPromoter Regions, GeneticRepetitive Sequences, Nucleic AcidSteroidogenic Factor 1Trans-ActivatorsTranscriptional ActivationConceptsElectrophoretic mobility shift assaysEnhancer sequencesCompetitive electrophoretic mobility shift assaysSupershift electrophoretic mobility shift assaysFunctional regulatory elementsGATA family membersMobility shift assaysGreater luciferase activityOrphan nuclear receptorSteroidogenic factor 1Luciferase reporter activityGATA sequencesFetoprotein transcription factorGATA familyChromatin immunoprecipitationTranscription factorsNuclear proteinsRegulatory elementsShift assaysRegulatory mechanismsFunctional analysisPromoter constructsDirect repeatsReporter activityUpstream region
2005
Flavin-containing monooxygenase genetic polymorphism: impact on chemical metabolism and drug development
Koukouritaki S, Hines R. Flavin-containing monooxygenase genetic polymorphism: impact on chemical metabolism and drug development. Pharmacogenomics 2005, 6: 807-822. PMID: 16296944, DOI: 10.2217/14622416.6.8.807.Peer-Reviewed Original ResearchDiscovery of Novel Flavin-Containing Monooxygenase 3 (FMO3) Single Nucleotide Polymorphisms and Functional Analysis of Upstream Haplotype Variants
Koukouritaki S, Poch M, Cabacungan E, McCarver D, Hines R. Discovery of Novel Flavin-Containing Monooxygenase 3 (FMO3) Single Nucleotide Polymorphisms and Functional Analysis of Upstream Haplotype Variants. Molecular Pharmacology 2005, 68: 383-392. PMID: 15858076, DOI: 10.1124/mol.105.012062.Peer-Reviewed Original ResearchConceptsFlavin-containing monooxygenasesFunctional analysisSingle nucleotide polymorphism (SNP) discoveryMembrane interaction domainHaplotype variantsSite-directed mutagenesisConsensus splice sitesFMO3 expressionUpstream SNPsGene functionPolymorphism discoveryNear complete lossRossmann foldFAD bindingInteraction domainSingle nucleotide polymorphismsRegion haplotypesHaplotype 8Exon SNPsFMO enzymesPromoter activityIntron SNPSequence analysisSNP frequenciesLuciferase construct
2003
Genetic Variability at the Human FMO1 Locus: Significance of a Basal Promoter Yin Yang 1 Element Polymorphism (FMO1*6)
Hines R, Luo Z, Hopp K, Cabacungan E, Koukouritaki S, McCarver D. Genetic Variability at the Human FMO1 Locus: Significance of a Basal Promoter Yin Yang 1 Element Polymorphism (FMO1*6). Journal Of Pharmacology And Experimental Therapeutics 2003, 306: 1210-1218. PMID: 12829732, DOI: 10.1124/jpet.103.053686.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphismsFlavin-containing monooxygenasesGenetic variabilityIntron 1 splice donor siteElectrophoretic mobility shift assaysYin Yang 1 (YY1) transcription factorTransient expression assaysCore binding sequenceATG start codonMobility shift assaysSplice donor siteCommon single nucleotide polymorphismsYY1 bindingStructural geneTranscription factorsStart codonShift assaysExonic sequencesChromosome 1q23Binding sequenceExpression assaysPromoter activityVariety of toxicantsBase pairsNucleotide polymorphisms