2021
Association of Apparent Treatment-Resistant Hypertension With Differential Risk of End-Stage Kidney Disease Across Racial Groups in the Million Veteran Program
Akwo EA, Robinson-Cohen C, Chung CP, Shah SC, Brown NJ, Ikizler TA, Wilson OD, Rowan BX, Shuey MM, Siew ED, Luther JM, Giri A, Hellwege JN, Edwards D, Roumie CL, Tao R, Tsao PS, Gaziano JM, Wilson PWF, O’Donnell C, Edwards TL, Kovesdy CP, Hung AM, Program O. Association of Apparent Treatment-Resistant Hypertension With Differential Risk of End-Stage Kidney Disease Across Racial Groups in the Million Veteran Program. Hypertension 2021, 78: 376-386. PMID: 34148359, PMCID: PMC8364328, DOI: 10.1161/hypertensionaha.120.16181.Peer-Reviewed Original Research
2020
Response to Letter to the Editor: “Hypertension and Type 2 Diabetes Are Associated With Decreased Inhibition of Dipeptidyl Peptidase-4 by Sitagliptin”
Wilson JR, Shuey MM, Brown NJ, Devin JK. Response to Letter to the Editor: “Hypertension and Type 2 Diabetes Are Associated With Decreased Inhibition of Dipeptidyl Peptidase-4 by Sitagliptin”. Journal Of The Endocrine Society 2020, 4: bvaa006. PMID: 32133430, PMCID: PMC7049288, DOI: 10.1210/jendso/bvaa006.Peer-Reviewed Original Research
2017
Hypertension and Type 2 Diabetes Are Associated With Decreased Inhibition of Dipeptidyl Peptidase-4 by Sitagliptin
Wilson JR, Shuey MM, Brown NJ, Devin JK. Hypertension and Type 2 Diabetes Are Associated With Decreased Inhibition of Dipeptidyl Peptidase-4 by Sitagliptin. Journal Of The Endocrine Society 2017, 1: 1168-1178. PMID: 29264572, PMCID: PMC5686657, DOI: 10.1210/js.2017-00312.Peer-Reviewed Original ResearchDPP4 activityHealthy controlsSitagliptin doseSystolic blood pressurePeptidase-4 inhibitorsType 2 diabetesDipeptidyl peptidase-4Blood pressureCrossover fashionMetabolic syndromeCrossover studyMultivariable analysisDPP4 inhibitionDPP4 inhibitorsHypertensionPlaceboPeptidase-4High dosesSitagliptinT2DMDecreased inhibitionPatientsLaboratory dataInfluences responseDiabetes
2014
Genetic variation in CYP4A11 and blood pressure response to mineralocorticoid receptor antagonism or ENaC inhibition: an exploratory pilot study in African Americans
Laffer CL, Elijovich F, Eckert GJ, Tu W, Pratt JH, Brown NJ. Genetic variation in CYP4A11 and blood pressure response to mineralocorticoid receptor antagonism or ENaC inhibition: an exploratory pilot study in African Americans. International Journal Of Cardiology Cardiovascular Risk And Prevention 2014, 8: 475-480. PMID: 25064769, PMCID: PMC4115247, DOI: 10.1016/j.jash.2014.04.011.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedBlack or African AmericanBlood PressureCytochrome P-450 CYP4ACytochrome P-450 Enzyme SystemDNADouble-Blind MethodFemaleGenetic VariationGenotypeHumansHypertensionMaleMiddle AgedMineralocorticoid Receptor AntagonistsPilot ProjectsRadioimmunoassayUnited StatesYoung AdultConceptsBlood pressure responseBlood pressureReceptor antagonismPressure responseMineralocorticoid receptor antagonismSalt-sensitive hypertensionAfrican AmericansExploratory pilot studyGC individualsAldosterone responseResistant hypertensionAntihypertensive effectTreatment responsePrecluded analysisCC genotypeCC homozygotesSpironolactoneC alleleHypertensionPilot studyENaC activationCYP4A11AmilorideActivation of ENaC.ENaC inhibition
2012
Polymorphisms in the serum- and glucocorticoid-inducible kinase 1 gene are associated with blood pressure and renin response to dietary salt intake
Rao AD, Sun B, Saxena A, Hopkins PN, Jeunemaitre X, Brown NJ, Adler GK, Williams JS. Polymorphisms in the serum- and glucocorticoid-inducible kinase 1 gene are associated with blood pressure and renin response to dietary salt intake. Journal Of Human Hypertension 2012, 27: 176-180. PMID: 22648267, PMCID: PMC3463709, DOI: 10.1038/jhh.2012.22.Peer-Reviewed Original ResearchMeSH KeywordsAdultBiomarkersBlood PressureChi-Square DistributionEuropeFemaleGene FrequencyGenetic Predisposition to DiseaseHumansHypertensionImmediate-Early ProteinsLinear ModelsLinkage DisequilibriumLogistic ModelsMaleMiddle AgedPhenotypePolymorphism, Single NucleotideProtein Serine-Threonine KinasesReninRenin-Angiotensin SystemSodium Chloride, DietaryUnited StatesWhite PeopleConceptsDietary salt intakeBlood pressureSalt intakeSingle nucleotide polymorphismsHigher systolic blood pressureMeasurement of BPAldosterone system activityRAA system activitySystem activitySystolic blood pressureSalt-sensitive hypertensionSGK1 gene variantGlucocorticoid-inducible kinase 1Non-significant trendNormotensive populationRenin responseEpithelial sodium channelHuman hypertensionGenotype statusStudy populationDistal nephronHypertensionAdditive genetic modelSodium channelsGene variantsLysine-Specific Demethylase 1: An Epigenetic Regulator of Salt-Sensitive Hypertension
Williams JS, Chamarthi B, Goodarzi MO, Pojoga LH, Sun B, Garza AE, Raby BA, Adler GK, Hopkins PN, Brown NJ, Jeunemaitre X, Ferri C, Fang R, Leonor T, Cui J, Guo X, Taylor KD, Chen Y, Xiang A, Raffel LJ, Buchanan TA, Rotter JI, Williams GH, Shi Y. Lysine-Specific Demethylase 1: An Epigenetic Regulator of Salt-Sensitive Hypertension. American Journal Of Hypertension 2012, 25: 812-817. PMID: 22534796, PMCID: PMC3721725, DOI: 10.1038/ajh.2012.43.Peer-Reviewed Original ResearchConceptsMinor allele carriersSalt-sensitive hypertensionBlood pressureSingle nuclear polymorphismsAllele carriersHypertensive cohortDietary saltWT miceLiberal salt dietLiberal salt intakeSystolic blood pressureSerum aldosterone concentrationHeterozygote knockout miceTranslational research studiesRenovascular responsivenessAldosterone concentrationSalt dietDietary sodiumSalt intakeSystolic BPHuman studiesHypertensionKnockout miceClinical relevanceCaucasian cohort
2011
CYP4A11 T8590C polymorphism, salt-sensitive hypertension, and renal blood flow
Williams JS, Hopkins PN, Jeunemaitre X, Brown NJ. CYP4A11 T8590C polymorphism, salt-sensitive hypertension, and renal blood flow. Journal Of Hypertension 2011, 29: 1913-1918. PMID: 21873888, PMCID: PMC3309034, DOI: 10.1097/hjh.0b013e32834aa786.Peer-Reviewed Original ResearchConceptsMean arterial pressureHigh salt intakeRenal blood flowHypertensive individualsBlood pressureSalt intakeC alleleSalt restrictionNormotensive individualsBlood flowSalt-sensitive blood pressureSalt sensitivityLow-salt dietDiagnosis of hypertensionHigh blood pressureSalt-sensitive hypertensionRenal vasodilationPressor responseSalt dietArterial pressureAngiotensin IIAttenuated increaseSodium homeostasisCYP4A11 T8590C polymorphismHypertensionRenin gene polymorphism: its relationship to hypertension, renin levels and vascular responses
Sun B, Williams JS, Pojoga L, Chamarthi B, Lasky-Su J, Raby BA, Hopkins PN, Jeunemaitre X, Brown NJ, Ferri C, Williams GH. Renin gene polymorphism: its relationship to hypertension, renin levels and vascular responses. Journal Of The Renin-Angiotensin-Aldosterone System 2011, 12: 564-571. PMID: 21490026, PMCID: PMC3444254, DOI: 10.1177/1470320311405873.Peer-Reviewed Original ResearchConceptsMean arterial pressurePlasma renin activityRenin activityRenin geneHypertension riskSingle nucleotide polymorphismsAngiotensin II infusionNormotensive Caucasian subjectsHyperPATH cohortII infusionPRA levelsVascular responsivenessRenin levelsArterial pressureEssential hypertensionVascular responsesAngiotensin IIHypertensionHigh riskIndependent cohortCaucasian subjectsA alleleResultant haplotypesUnderlying mechanismGene variationThis is not Dr. Conn's aldosterone anymore.
Brown NJ. This is not Dr. Conn's aldosterone anymore. Transactions Of The American Clinical And Climatological Association 2011, 122: 229-43. PMID: 21686229, PMCID: PMC3116341.Peer-Reviewed Original ResearchMeSH KeywordsAldosteroneAngiotensin IIAngiotensin II Type 1 Receptor BlockersAngiotensin-Converting Enzyme InhibitorsAnimalsBlood PressureCytochrome P-450 CYP11B2Disease Models, AnimalEnzyme InhibitorsFibrosisGene Expression RegulationHumansHyperaldosteronismInflammation MediatorsKidneyLigandsMiceMineralocorticoid Receptor AntagonistsMyocardiumRatsReceptors, MineralocorticoidSignal TransductionTime FactorsConceptsMR-independent pathwayPrevalence of hyperaldosteronismAngiotensin receptor blockersMineralocorticoid receptor antagonismSecretion of aldosteroneAldosterone-secreting adenomasPro-fibrotic effectsReceptor blockersResistant hypertensionSevere hypertensionAldosterone concentrationRenal injuryEndogenous aldosteroneACE inhibitorsCardiovascular remodelingAngiotensin IIReceptor antagonismHeart diseaseProfibrotic effectsAldosteroneBaseline valuesEnzyme inhibitorsPatientsPotassium homeostasisHypertension
2008
Association of a CYP4A11 Variant and Blood Pressure in Black Men
Gainer JV, Lipkowitz MS, Yu C, Waterman MR, Dawson EP, Capdevila JH, Brown NJ, Group A. Association of a CYP4A11 Variant and Blood Pressure in Black Men. Journal Of The American Society Of Nephrology 2008, 19: 1606-1612. PMID: 18385420, PMCID: PMC2488260, DOI: 10.1681/asn.2008010063.Peer-Reviewed Original ResearchConceptsHypertensive renal diseaseRenal diseaseClinical outcomesHigher systolic BPAdverse clinical outcomesWhite individualsRegulation of BPEndogenous arachidonic acidBlack menBaseline proteinuriaCYP4A11 variantsHypertensive nephrosclerosisRenal vasoconstrictorClinical characteristicsCumulative incidenceRenal functionBlood pressureDiastolic BPHigher systolicSystolic BPHigh BPKidney diseasePulse pressureMale miceHypertension
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 variantsUrinary Free Cortisol: An Intermediate Phenotype and a Potential Genetic Marker for a Salt-Resistant Subset of Essential Hypertension
Chamarthi B, Kolatkar NS, Hunt SC, Williams JS, Seely EW, Brown NJ, Murphey LJ, Jeunemaitre X, Williams GH. Urinary Free Cortisol: An Intermediate Phenotype and a Potential Genetic Marker for a Salt-Resistant Subset of Essential Hypertension. The Journal Of Clinical Endocrinology & Metabolism 2007, 92: 1340-1346. PMID: 17264181, DOI: 10.1210/jc.2006-2093.Peer-Reviewed Original ResearchConceptsUrinary free cortisolEssential hypertensionHigh urinary free cortisolLow-salt dietMean arterial pressureIntermediate phenotypesStrong familial componentArterial pressureDietary sodiumBlood pressureFree cortisolHypertensive siblingsHypertensionHypertensivesNormotensivesGeneral communityHypertensive familiesFamilial componentPreliminary reportFamilial aggregationSignificant predictorsPotential genetic markersSignificant differencesSignificant proportionCortisolAla92 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 ResearchConceptsDevelopment 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
2005
Single 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
Functional Variant of CYP4A11 20-Hydroxyeicosatetraenoic Acid Synthase Is Associated With Essential Hypertension
Gainer JV, Bellamine A, Dawson EP, Womble KE, Grant SW, Wang Y, Cupples LA, Guo CY, Demissie S, O’Donnell C, Brown NJ, Waterman MR, Capdevila JH. Functional Variant of CYP4A11 20-Hydroxyeicosatetraenoic Acid Synthase Is Associated With Essential Hypertension. Circulation 2004, 111: 63-69. PMID: 15611369, DOI: 10.1161/01.cir.0000151309.82473.59.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAllelesAmino Acid SubstitutionArachidonic AcidBlack PeopleBlood PressureCodonCohort StudiesComorbidityCytochrome P-450 CYP4ACytochrome P-450 Enzyme SystemDNA Mutational AnalysisFemaleGene FrequencyGenetic Predisposition to DiseaseGenetic VariationGenotypeHumansHydroxyeicosatetraenoic AcidsHypertensionIntronsKidneyLauric AcidsMaleMiddle AgedMultifactorial InheritanceMutagenesis, InsertionalMutation, MissensePoint MutationSequence DeletionTennesseeUnited StatesWhite PeopleConceptsArachidonic acidORs of hypertensionBlood pressure controlBody mass indexEndogenous arachidonic acidLarge population databaseFramingham Heart StudySevere hypertensionEssential hypertensionHypertension comorbidityTubular functionHypertensive statusMass indexFunctional variantsHypertensionHeart StudyPressure controlCYP4A11Polygenic determinantsPopulation databaseTargeted disruptionHuman CYP4A11Acid synthaseAssociationSynthase activity
2003
Eplerenone
Brown NJ. Eplerenone. Circulation 2003, 107: 2512-2518. PMID: 12756192, DOI: 10.1161/01.cir.0000071081.35693.9a.Peer-Reviewed Original ResearchConceptsAldosterone receptor antagonistsReceptor antagonistMineralocorticoid receptor-dependent mechanismSelective aldosterone receptor antagonistAldosterone receptor antagonismRole of aldosteroneCongestive heart failureTreatment of hypertensionReceptor-dependent mechanismAntiandrogenic side effectsRenal injuryHeart failureReceptor antagonismCardiovascular toxicityClinical trialsSide effectsAnimal studiesEplerenoneAldosteroneAntagonistHypertensionPatientsSpironolactoneInjuryMortality
2002
G protein-coupled receptor kinase 4 gene variants in human essential hypertension
Felder RA, Sanada H, Xu J, Yu PY, Wang Z, Watanabe H, Asico LD, Wang W, Zheng S, Yamaguchi I, Williams SM, Gainer J, Brown NJ, Hazen-Martin D, Wong LJ, Robillard JE, Carey RM, Eisner GM, Jose PA. G protein-coupled receptor kinase 4 gene variants in human essential hypertension. Proceedings Of The National Academy Of Sciences Of The United States Of America 2002, 99: 3872-3877. PMID: 11904438, PMCID: PMC122616, DOI: 10.1073/pnas.062694599.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood PressureBody WeightCells, CulturedCHO CellsCricetinaeCyclic AMPFemaleG-Protein-Coupled Receptor Kinase 4Heart RateHeterotrimeric GTP-Binding ProteinsHumansHypertensionImmunohistochemistryKidney Function TestsKidney Tubules, ProximalMaleMiceMice, TransgenicOrgan SizePolymorphism, Single NucleotideProtein Serine-Threonine KinasesReceptors, Dopamine D1Signal TransductionConceptsHuman essential hypertensionEssential hypertensionGenetic hypertensionProximal tubulesG-protein-coupled receptor kinase activityEnzyme complexUrinary sodium excretionRenal dopaminergic systemG protein-coupled receptor kinasesProtein-coupled receptor kinasesWild-type geneAbility of dopamineRenal proximal tubulesReceptor kinase activitySodium excretionDopaminergic actionsHypotensive effectChinese hamster ovary cellsDopamine receptorsDopaminergic systemHypertensionLike agonistsElectrolyte balanceTransgenic miceHamster ovary cells
2000
Human β2‐adrenergic receptor polymorphisms: No association with essential hypertension in black or white Americans
Xie H, Stein C, Kim R, Gainer J, Sofowora G, Dishy V, Brown N, Goree R, Haines J, Wood A. Human β2‐adrenergic receptor polymorphisms: No association with essential hypertension in black or white Americans. Clinical Pharmacology & Therapeutics 2000, 67: 670-675. PMID: 10872649, DOI: 10.1067/mcp.2000.106293.Peer-Reviewed Original ResearchConceptsHypertensive subjectsEssential hypertensionGlu27 alleleBeta2-adrenergic receptor genotypesBeta2-adrenergic receptor polymorphismsWhite subjectsReceptor variantsBeta2-adrenergic receptor geneNormotensive white subjectsPresence of hypertensionBlack subjectsHomozygous genotypeBeta2-adrenergic receptorCommon genetic polymorphismsHypertensive groupNormotensive subjectsBlood pressurePopulation-based case-control association studiesVascular responsesCase-control association studyReceptor polymorphismsReceptor genotypeHypertensionReceptor responsesHuman beta2-adrenergic receptor
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 polymorphismα1A-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. DOI: 10.1097/01213011-199910000-00012.Peer-Reviewed Original ResearchΑ1A-ARAfrican AmericansPrevalence of hypertensionPathogenesis of hypertensionVascular smooth muscleΑ1-adrenergic receptorsΑ1-adrenergic responsesCaucasian individualsEthnic differencesΑ1-AR subtypesVasoconstrictor sensitivityVascular reactivityBlood pressureEssential hypertensionHypertensive individualsVascular responsesVascular toneΑ1-ARReceptor polymorphismsSmooth muscleHypertensionSignificant intergenotypic differencesPotential roleRestriction fragment length polymorphismAllelic distribution