2017
Association of gain-of-function EPHX2 polymorphism Lys55Arg with acute kidney injury following cardiac surgery
Shuey MM, Billings FT, Wei S, Milne GL, Nian H, Yu C, Brown NJ. Association of gain-of-function EPHX2 polymorphism Lys55Arg with acute kidney injury following cardiac surgery. PLOS ONE 2017, 12: e0175292. PMID: 28552948, PMCID: PMC5446112, DOI: 10.1371/journal.pone.0175292.Peer-Reviewed Original ResearchConceptsAcute kidney injuryChronic kidney diseaseCardiac surgery cohortSoluble epoxide hydrolaseCardiac surgeryKidney injurySurgery cohortAcute Kidney Injury Network criteriaIncidence of AKIPostoperative acute kidney injuryPercent of patientsGlomerular filtration rateBody mass indexAssociation of gainsRenal injuryCardiopulmonary bypassWhite patientsMass indexKidney diseaseFiltration ratePharmacological strategiesDiscovery cohortNetwork criteriaVariant carriersSEH activity
2012
Polymorphisms in the transcription factor NRF2 and forearm vasodilator responses in humans
Marczak ED, Marzec J, Zeldin DC, Kleeberger SR, Brown NJ, Pretorius M, Lee CR. Polymorphisms in the transcription factor NRF2 and forearm vasodilator responses in humans. Pharmacogenetics And Genomics 2012, 22: 620-628. PMID: 22668754, PMCID: PMC3599320, DOI: 10.1097/fpc.0b013e32835516e5.Peer-Reviewed Original ResearchConceptsForearm vascular resistanceForearm blood flowVariant allele carriersVasodilator responseSodium nitroprussideVascular functionAllele carriersStrain-gauge venous occlusion plethysmographyLower forearm blood flowEndothelial-independent mannerForearm vasodilator responseVenous occlusion plethysmographyWild-type individualsTranscription factor Nrf2Endothelial dysfunctionOcclusion plethysmographyVascular resistanceIncremental dosesCardiovascular diseaseBlood flowG genotypeA polymorphismSignificant associationBasal conditionsFactor Nrf2
2011
Epistatic Interactions in Genetic Regulation of t-PA and PAI-1 Levels in a Ghanaian Population
Penrod NM, Poku KA, Vaughn D, Asselbergs FW, Brown NJ, Moore JH, Williams SM. Epistatic Interactions in Genetic Regulation of t-PA and PAI-1 Levels in a Ghanaian Population. PLOS ONE 2011, 6: e16639. PMID: 21304999, PMCID: PMC3031598, DOI: 10.1371/journal.pone.0016639.Peer-Reviewed Original ResearchConceptsEpistatic interactionsPAI-1 levelsRenin-angiotensin systemMultiple genetic effectsPathway-specific genesD polymorphismPAI-1Genetic architectureT-PASingle SNP analysisGenetic regulationCentral genesSpecific genesCardiovascular diseaseFibrinolytic systemSNP analysisGenetic effectsGenesCleavage of angiotensinogenPlasminogen activator inhibitor-1Plasma t-PAT-PA levelsTissue plasminogen activatorActivator inhibitor-1Enzyme cleavage
2008
Male–female differences in the genetic regulation of t-PA and PAI-1 levels in a Ghanaian population
Schoenhard JA, Asselbergs FW, Poku KA, Stocki SA, Gordon S, Vaughan DE, Brown NJ, Moore JH, Williams SM. Male–female differences in the genetic regulation of t-PA and PAI-1 levels in a Ghanaian population. Human Genetics 2008, 124: 479-488. PMID: 18953568, PMCID: PMC2770717, DOI: 10.1007/s00439-008-0573-x.Peer-Reviewed Original ResearchConceptsPlasminogen activator inhibitor-1PAI-1 levelsTissue-type plasminogen activatorRenin polymorphismPAI-1 4G/5G polymorphismRenin-angiotensin systemDiastolic blood pressurePopulation-based sampleActivator inhibitor-1Large-scale population-based samplePAI-1 expressionBlood pressureTotal cholesterolThromboembolic diseasePlasma levelsRisk factorsCardiovascular diseaseD polymorphismMetabolic parametersG polymorphismFibrinolytic systemGene polymorphismsThrombus formationCaucasian subjectsGhanaian populationBradykinin Type 2 Receptor BE1 Genotype Influences Bradykinin-Dependent Vasodilation During Angiotensin-Converting Enzyme Inhibition
Van Guilder GP, Pretorius M, Luther JM, Byrd JB, Hill K, Gainer JV, Brown NJ. Bradykinin Type 2 Receptor BE1 Genotype Influences Bradykinin-Dependent Vasodilation During Angiotensin-Converting Enzyme Inhibition. Hypertension 2008, 51: 454-459. PMID: 18180402, PMCID: PMC2581632, DOI: 10.1161/hypertensionaha.107.102574.Peer-Reviewed Original ResearchMeSH KeywordsAdultAngiotensin-Converting Enzyme InhibitorsBlood PressureBradykininDrug SynergismEnalaprilatEndothelium, VascularFemaleForearmGenotypeHumansInjections, Intra-ArterialMaleMethacholine ChlorideNitroprussidePolymorphism, GeneticReceptor, Bradykinin B2Regional Blood FlowSex FactorsTissue Plasminogen ActivatorVascular ResistanceVasodilationVasodilator AgentsConceptsForearm blood flowT-PA releaseForearm vascular resistanceVascular resistanceBlood flowBlood pressureTissue-type plasminogen activator releaseBasal forearm blood flowAngiotensin-Converting Enzyme InhibitionGenotype groupsNet t-PA releaseReceptor-mediated vasodilationBasal forearm vascular resistanceSystolic blood pressureBody mass indexIntra-arterial bradykininEffect of bradykininDegradation of bradykininPlasminogen activator releaseEnzyme inhibitionMass indexVascular responsesActivator releaseBradykininWhite American subjects
2007
Functional BSND Variants in Essential Hypertension*
Sile S, Gillani NB, Velez DR, Vanoye CG, Yu C, Byrne LM, Gainer JV, Brown NJ, Williams SM, George AL. Functional BSND Variants in Essential Hypertension*. American Journal Of Hypertension 2007, 20: 1176-1182. PMID: 17954364, DOI: 10.1016/j.amjhyper.2007.07.003.Peer-Reviewed Original ResearchConceptsThick ascending limbControl populationNormotensive control populationSodium chloride reabsorptionClC-Kb chloride channelsBlood pressure regulationLogistic regression analysisRenal salt reabsorptionChloride channelsNormotensive populationEssential hypertensionChloride reabsorptionHomogenous cohortStudy populationHypertensionAscending limbGhanaian subjectsSalt reabsorptionHispanic subjectsClC-KbCaucasian populationPartial lossSingle nucleotide polymorphismsRegression analysisRare variantsThe Bradykinin Type 2 Receptor BE1 Polymorphism and Ethnicity Influence Systolic Blood Pressure and Vascular Resistance
Pretorius MM, Gainer JV, Van Guilder GP, Coelho EB, Luther JM, Fong P, Rosenbaum DD, Malave HA, Yu C, Ritchie MD, Vaughan DE, Brown NJ. The Bradykinin Type 2 Receptor BE1 Polymorphism and Ethnicity Influence Systolic Blood Pressure and Vascular Resistance. Clinical Pharmacology & Therapeutics 2007, 83: 122-129. PMID: 17522594, DOI: 10.1038/sj.clpt.6100250.Peer-Reviewed Original ResearchMeSH KeywordsAdultBlack or African AmericanBlood Flow VelocityBlood PressureBradykininDose-Response Relationship, DrugFemaleForearmGene FrequencyGenotypeHumansInfusions, Intra-ArterialMaleNitroprussidePhenotypePolymorphism, GeneticReceptor, Bradykinin B2Regional Blood FlowVascular ResistanceVasodilator AgentsWhite PeopleConceptsSystolic blood pressureForearm vascular resistanceVascular resistanceBlood pressureEndothelium-independent agonist sodium nitroprussideEndothelium-dependent agonist bradykininIntrabrachial artery infusionsLeft ventricular massBradykinin B2 receptor geneB2 receptor geneNormotensive subjectsVentricular massPulse pressureB2 receptorsAgonist bradykininSodium nitroprussideReceptor geneBradykininGroupPolymorphismInfusionWhite AmericansNitroprussideBaselineBlack AmericansAla92 Type 2 Deiodinase Allele Increases Risk for the Development of Hypertension
Gumieniak O, Perlstein TS, Williams JS, Hopkins PN, Brown NJ, Raby BA, Williams GH. Ala92 Type 2 Deiodinase Allele Increases Risk for the Development of Hypertension. Hypertension 2007, 49: 461-466. PMID: 17224473, DOI: 10.1161/01.hyp.0000256295.72185.fd.Peer-Reviewed Original ResearchMeSH KeywordsAdultAllelesFemaleGenetic Predisposition to DiseaseHumansHypertensionIodide PeroxidaseMaleMiddle AgedPolymorphism, GeneticConceptsDevelopment of hypertensionType 2 iodothyronine deiodinaseNormotensive subjectsIodothyronine deiodinaseConversion of thyroxineSequenom MassARRAY platformEuthyroid adultsThr92Ala polymorphismEuthyroid subjectsOdds ratioHypertensionPeripheral tissuesAllele carriersIncrease riskMassARRAY platformInfluence susceptibilityHypertension susceptibilityThyroid pathwaysIntermediate phenotypesPresent studyNonsynonymous polymorphismsSubjectsDeiodinaseRiskAllele frequencies
2006
β-2 Adrenergic Receptor Diplotype Defines a Subset of Salt-Sensitive Hypertension
Pojoga L, Kolatkar NS, Williams JS, Perlstein TS, Jeunemaitre X, Brown NJ, Hopkins PN, Raby BA, Williams GH. β-2 Adrenergic Receptor Diplotype Defines a Subset of Salt-Sensitive Hypertension. Hypertension 2006, 48: 892-900. PMID: 17015767, DOI: 10.1161/01.hyp.0000244688.45472.95.Peer-Reviewed Original ResearchConceptsBlood pressure responseSalt-sensitive hypertensionBeta-2 adrenergic receptorsAldosterone secretionDietary sodiumAdrenergic receptorsGreater blood pressure responseAdrenergic receptor variantsHigh plasma aldosteroneLow plasma reninLow-sodium balanceNormotensive white subjectsMean arterial pressureLow-renin hypertensionSerum potassium levelsAdrenergic receptor genotypePressure responseBlood pressure evaluationAdrenergic receptor stimulationAldosterone responseAldosterone systemHypertensive subjectsNormotensive subjectsPlasma aldosteronePlasma renin
2005
The Kallikrein-Kinin System: Current and Future Pharmacological Targets
Moreau ME, Garbacki N, Molinaro G, Brown NJ, Marceau F, Adam A. The Kallikrein-Kinin System: Current and Future Pharmacological Targets. Journal Of Pharmacological Sciences 2005, 99: 6-38. PMID: 16177542, DOI: 10.1254/jphs.srj05001x.Peer-Reviewed Original ResearchMeSH KeywordsAngioedemaAngiotensin-Converting Enzyme InhibitorsAnimalsAprotininBradykininBradykinin B2 Receptor AntagonistsCardiovascular DiseasesComplement C1 Inactivator ProteinsComplement C1 Inhibitor ProteinHumansInflammationKallikrein-Kinin SystemKallikreinsKidney DiseasesKininsNeprilysinPeptidyl-Dipeptidase APolymorphism, GeneticPyridinesRandomized Controlled Trials as TopicReceptor, Bradykinin B1Receptor, Bradykinin B2SerpinsThiazepinesConceptsKallikrein-kinin systemMultiple pharmacological interventionsPrecursors of kininsFuture pharmacological targetsProinflammatory effectsVasoactive kininsPharmacological interventionsCardiovascular propertiesPharmacological targetsComplement pathwayKininsActive kininsPathological processesPharmacological activitiesPlasma kallikreinMetabolic cascadeImportant metabolic pathwaysMetabolic pathwaysAntiproteasesSingle nucleotide polymorphisms in the CYP2J2 and CYP2C8 genes and the risk of hypertension
King LM, Gainer JV, David GL, Dai D, Goldstein JA, Brown NJ, Zeldin DC. Single nucleotide polymorphisms in the CYP2J2 and CYP2C8 genes and the risk of hypertension. Pharmacogenetics And Genomics 2005, 15: 7-13. PMID: 15864120, DOI: 10.1097/01213011-200501000-00002.Peer-Reviewed Original ResearchMeSH KeywordsAdultAllelesArginineAryl Hydrocarbon HydroxylasesCytochrome P-450 CYP2C8Cytochrome P-450 CYP2J2Cytochrome P-450 Enzyme SystemElectrolytesFemaleGenotypeHumansHypertensionLinkage DisequilibriumLysineMaleMiddle AgedOdds RatioOxygenasesPharmacogeneticsPolymorphism, GeneticPolymorphism, Single NucleotideRiskSex FactorsConceptsFamily historyVariant allele frequencyCaucasian maleGenotype distributionVariant allelesArachidonic acidRisk of hypertensionBody mass indexAdditional subgroup analysesAfrican AmericansCis-epoxyeicosatrienoic acidsBiethnic populationNormotensive CaucasiansHypertensive subjectsAllele frequenciesMass indexVascular toneHypertension riskHypertension statusSubgroup analysisOdds ratioHypertensionProtective effectCYP2C8 geneCYP2J2
2004
Relationship Between Carbamoyl-Phosphate Synthetase Genotype and Systemic Vascular Function
Summar ML, Gainer JV, Pretorius M, Malave H, Harris S, Hall LD, Weisberg A, Vaughan DE, Christman BW, Brown NJ. Relationship Between Carbamoyl-Phosphate Synthetase Genotype and Systemic Vascular Function. Hypertension 2004, 43: 186-191. PMID: 14718356, DOI: 10.1161/01.hyp.0000112424.06921.52.Peer-Reviewed Original ResearchConceptsForearm blood flowNitric oxide metabolite concentrationsNitric oxide metabolitesBlood flowOxide metabolitesNitric oxide-mediated vasodilationVascular smooth muscle reactivityAllele homozygotesTissue-type plasminogen activator antigenSystemic vascular functionSmooth muscle reactivityPlasminogen activator antigenC allele homozygotesNitric oxide productionMetabolite concentrationsVasodilator responseBrachial arteryMuscle reactivityVascular functionHealthy subjectsBlood samplesSodium nitroprussideC alleleOxide productionCarbamoyl phosphate synthetase 1
2002
The relationship between plasma t‐PA and PAI‐1 levels is dependent on epistatic effects of the ACE I/D and PAI‐1 4G/5G polymorphisms
Moore J, Smolkin M, Lamb J, Brown N, Vaughan D. The relationship between plasma t‐PA and PAI‐1 levels is dependent on epistatic effects of the ACE I/D and PAI‐1 4G/5G polymorphisms. Clinical Genetics 2002, 62: 53-59. PMID: 12123488, DOI: 10.1034/j.1399-0004.2002.620107.x.Peer-Reviewed Original ResearchA comparison of combinatorial partitioning and linear regression for the detection of epistatic effects of the ACE I/D and PAI‐1 4G/5G polymorphisms on plasma PAI‐1 levels
Moore J, Lamb J, Brown N, Vaughan D. A comparison of combinatorial partitioning and linear regression for the detection of epistatic effects of the ACE I/D and PAI‐1 4G/5G polymorphisms on plasma PAI‐1 levels. Clinical Genetics 2002, 62: 74-79. PMID: 12123491, DOI: 10.1034/j.1399-0004.2002.620110.x.Peer-Reviewed Original ResearchComparative Effects of Estrogen and Angiotensin-Converting Enzyme Inhibition on Plasminogen Activator Inhibitor-1 in Healthy Postmenopausal Women
Brown NJ, Abbas A, Byrne D, Schoenhard JA, Vaughan DE. Comparative Effects of Estrogen and Angiotensin-Converting Enzyme Inhibition on Plasminogen Activator Inhibitor-1 in Healthy Postmenopausal Women. Circulation 2002, 105: 304-309. PMID: 11804984, DOI: 10.1161/hc0302.102570.Peer-Reviewed Original ResearchMeSH KeywordsAldosteroneAngiotensin IIAngiotensin-Converting Enzyme InhibitorsBlood PressureCardiovascular DiseasesCross-Over StudiesDrug Therapy, CombinationEstradiolEstrogen Replacement TherapyEstrogens, Conjugated (USP)FemaleHumansMiddle AgedPlasminogen Activator Inhibitor 1Polymorphism, GeneticPostmenopauseRamiprilReninSingle-Blind MethodTissue Plasminogen ActivatorConceptsHealthy postmenopausal womenPAI-1 4G/5G genotypePlasma renin activityPostmenopausal womenPAI-1 concentrationsACE inhibitionTissue plasminogen activatorConjugated estrogensPAI-1G genotypeRenin activityAngiotensin IIPlasminogen activator inhibitor-1 (PAI-1) concentrationsAngiotensin-Converting Enzyme InhibitionPAI-1 antigen concentrationsPlasminogen activatorConjugated equine estrogensEffects of estrogenPlasminogen activator inhibitor-1Activator inhibitor-1Combination estrogenClinical outcomesEquine estrogensCombined therapyCrossover treatment
2001
Interactive Effect of PAI-1 4G/5G Genotype and Salt Intake on PAI-1 Antigen
Brown N, Murphey L, Srikuma N, Koschachuhanan N, Williams G, Vaughan D. Interactive Effect of PAI-1 4G/5G Genotype and Salt Intake on PAI-1 Antigen. Arteriosclerosis Thrombosis And Vascular Biology 2001, 21: 1071-1077. PMID: 11397722, DOI: 10.1161/01.atv.21.6.1071.Peer-Reviewed Original ResearchConceptsPAI-1 4G/5G genotypePAI-1 antigen concentrationsPAI-1 antigenHigh salt intakeLow salt intakeSalt intakeG genotypeAntigen concentrationThrombotic cardiovascular eventsPlasma renin activityPAI-1 expressionPAI-1 geneAldosterone systemCardiovascular eventsCardiovascular morbidityRenin activityPharmacological therapyEssential hypertensionSerum triglyceridesEffects of activationG polymorphismG homozygotesG groupAntigenIntakePreprescription Genotyping
Roden D, Brown N. Preprescription Genotyping. Circulation 2001, 103: 1608-1610. PMID: 11273984, DOI: 10.1161/01.cir.103.12.1608.Peer-Reviewed Original Research
2000
Altered frequency of a promoter polymorphism of the kinin B2 receptor gene in hypertensive African-Americans*
Gainer J, Brown N, Bachvarova M, Bastien L, Maltais I, Marceau F, Bachvarov D. Altered frequency of a promoter polymorphism of the kinin B2 receptor gene in hypertensive African-Americans*. American Journal Of Hypertension 2000, 13: 1268-1273. PMID: 11130770, DOI: 10.1016/s0895-7061(00)01215-2.Peer-Reviewed Original ResearchAngiotensin-Converting Enzyme Insertion/Deletion Polymorphism Modulates the Human In Vivo Metabolism of Bradykinin
Murphey L, Gainer J, Vaughan D, Brown N. Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism Modulates the Human In Vivo Metabolism of Bradykinin. Circulation 2000, 102: 829-832. PMID: 10952948, DOI: 10.1161/01.cir.102.8.829.Peer-Reviewed Original ResearchConceptsPlasma ACE activityACE activityInsertion/deletion polymorphismD genotypeD alleleBK1-5ACE I/D polymorphismEnzyme insertion/deletion polymorphismAngiotensin-Converting Enzyme Insertion/Deletion PolymorphismTissue plasminogen activator releaseAngiotensin II productionDeletion polymorphismTissue ACE activityACE D alleleACE I/IPlasminogen activator releaseFmol/mLPlasma ACE levelsBradykinin metabolismBrachial arteryVenous returnCardioprotective peptideKinin concentrationsACE levelsBradykinin concentrations
1999
α1A-Adrenergic receptor polymorphism
Xie H, Kim R, Stein C, Gainer J, Brown N, Wood A. α1A-Adrenergic receptor polymorphism. Pharmacogenetics And Genomics 1999, 9: 651-656. PMID: 10591546, DOI: 10.1097/00008571-199910000-00012.Peer-Reviewed Original ResearchConceptsAlpha1A-ARAfrican AmericansPrevalence of hypertensionPathogenesis of hypertensionAlpha1-adrenergic receptorsAlpha1-AR subtypesVascular smooth muscleCaucasian individualsEthnic differencesVasoconstrictor sensitivityVascular reactivityAlpha1-ARBlood pressureEssential hypertensionHypertensive individualsVascular responsesVascular toneReceptor polymorphismsSmooth muscleHypertensionSignificant intergenotypic differencesPotential roleRestriction fragment length polymorphismAllelic distributionFragment length polymorphism