2011
Renin 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 variation
2008
The T8590C Polymorphism of CYP4A11 and 20-Hydroxyeicosatetraenoic Acid in Essential Hypertension
Laffer CL, Gainer JV, Waterman MR, Capdevila JH, Laniado-Schwartzman M, Nasjletti A, Brown NJ, Elijovich F. The T8590C Polymorphism of CYP4A11 and 20-Hydroxyeicosatetraenoic Acid in Essential Hypertension. Hypertension 2008, 51: 767-772. PMID: 18227405, PMCID: PMC2365894, DOI: 10.1161/hypertensionaha.107.102921.Peer-Reviewed Original ResearchConceptsBlood pressureC carriersHypertensive subjectsSalt-sensitive hypertensive subjectsHigher diastolic blood pressureT8590C polymorphismSalt-sensitive subjectsDiastolic blood pressureMicroU/mLDahl S ratsSerum insulin concentrationsC allele carriersC allele frequencySalt sensitivityPressure natriuresisEssential hypertensionFractional excretionSerum insulinHip ratioHuman hypertensionInsulin resistanceInsulin sensitivitySodium balanceInsulin concentrationsTT 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 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 proportionCortisol
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
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
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 groupAntigenIntake
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
1998
Angiotensin-Converting Enzyme Inhibitors
Brown N, Vaughan D. Angiotensin-Converting Enzyme Inhibitors. Circulation 1998, 97: 1411-1420. PMID: 9577953, DOI: 10.1161/01.cir.97.14.1411.Peer-Reviewed Original ResearchConceptsACE inhibitorsVentricular dysfunctionMyocardial infarctionAngiotensin AT1 receptor antagonistAngiotensin converting enzyme (ACE) inhibitorsTissue-bound ACESystemic vascular resistanceCongestive heart failureAT1 receptor antagonistTreatment of hypertensionRoute of eliminationVascular resistanceCardiovascular mortalityDiabetic nephropathyEssential hypertensionHeart failureNatriuretic propertiesRenal diseaseVasoactive substancesAngiotensin IIReceptor antagonistHeart rateSide effectsEnzyme inhibitorsHypertrophic properties
1997
Plasminogen actiwator inhibitor type 1 in diabetes and hypertension
Litchfield W, Brown N, Vaughan D. Plasminogen actiwator inhibitor type 1 in diabetes and hypertension. Current Opinion In Endocrinology Diabetes And Obesity 1997, 4: 233-238. DOI: 10.1097/00060793-199706000-00009.Peer-Reviewed Original ResearchCardiovascular riskPAI-1Inhibitor type 1Type 1Elevated levelsIncreased cardiovascular riskRenin-angiotensin systemEndogenous fibrinolytic systemPlasminogen activator inhibitor type 1Activator inhibitor type 1Tissue plasminogen activatorHypertensive patientsEssential hypertensionMyocardial infarctionCardiovascular diseaseFibrinolytic systemHypertensionPlasminogen activatorStrong associationIncidenceRiskPrimary inhibitorHyperinsulinemiaHypertriglyceridemiaInfarction
1996
Increased sensitivity to bradykinin among African Americans
Gainer J, Nadeau J, Ryder D, Brown N. Increased sensitivity to bradykinin among African Americans. Journal Of Allergy And Clinical Immunology 1996, 98: 283-287. PMID: 8757204, DOI: 10.1016/s0091-6749(96)70151-3.Peer-Reviewed Original ResearchConceptsKallikrein-kinin systemWheal responseAfrican AmericansLife-threatening side effectsTissue kallikrein-kinin systemACE inhibitor-associated angioedemaACE inhibitor doseMechanisms of angioedemaDouble-blind fashionDoses of bradykininAfrican American raceNormotensive African AmericansUrinary kallikrein levelsACE inhibitor-induced increaseInhibitor-induced increaseBradykinin doseConcurrent medicationsEssential hypertensionKallikrein levelsBradykinin levelsExogenous bradykininIntradermal injectionAmerican raceSide effectsInhibitor dose