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
2017
Genetic Effects on the Correlation Structure of CVD Risk Factors Exome-Wide Data From a Ghanaian Population
Kodaman N, Sobota RS, Asselbergs FW, Oetjens MT, Moore JH, Brown NJ, Aldrich MC, Williams SM. Genetic Effects on the Correlation Structure of CVD Risk Factors Exome-Wide Data From a Ghanaian Population. Global Heart 2017, 12: 133-140. PMID: 28408189, PMCID: PMC5642993, DOI: 10.1016/j.gheart.2017.01.013.Peer-Reviewed Original ResearchConceptsPlasminogen activator inhibitor-1CVD risk factorsRisk factorsCardiovascular disease risk factorsDisease risk factorsHigh blood pressureActivator inhibitor-1Dissolution of thrombusArterial pressureBlood pressureMyocardial infarctionPlasma concentrationsStudy participantsGhanaian populationInhibitor-1Significant heterogeneityHeterogeneity of correlationAfrican AmericansGenetic variantsGenetic association studiesDirect roleAssociation 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
2015
A prevalent caveolin-1 gene variant is associated with the metabolic syndrome in Caucasians and Hispanics
Baudrand R, Goodarzi MO, Vaidya A, Underwood PC, Williams JS, Jeunemaitre X, Hopkins PN, Brown N, Raby BA, Lasky-Su J, Adler GK, Cui J, Guo X, Taylor KD, Chen YD, Xiang A, Raffel LJ, Buchanan TA, Rotter JI, Williams GH, Pojoga LH. A prevalent caveolin-1 gene variant is associated with the metabolic syndrome in Caucasians and Hispanics. Metabolism 2015, 64: 1674-1681. PMID: 26475177, PMCID: PMC4641791, DOI: 10.1016/j.metabol.2015.09.005.Peer-Reviewed Original ResearchConceptsMinor allele carriersAllele carriersMetabolic syndromeInsulin resistanceHigher oddsHigher Framingham risk scoreFramingham risk scoreGene variantsNon-obese subjectsMinor allele carrier statusAllele carrier statusHyperPATH cohortLow HDLMetS diagnosisMetS riskObese subjectsMulticenter studyObesity statusSimilar BMIRisk scoreHispanic cohortClinical implicationsHispanic participantsCohortCarrier status
2014
Arg287Gln variant of EPHX2 and epoxyeicosatrienoic acids are associated with insulin sensitivity in humans
Ramirez CE, Shuey MM, Milne GL, Gilbert K, Hui N, Yu C, Luther JM, Brown NJ. Arg287Gln variant of EPHX2 and epoxyeicosatrienoic acids are associated with insulin sensitivity in humans. Prostaglandins And Other Lipid Mediators 2014, 113: 38-44. PMID: 25173047, PMCID: PMC4253976, DOI: 10.1016/j.prostaglandins.2014.08.001.Peer-Reviewed Original ResearchConceptsInsulin sensitivity indexEpoxyeicosatrienoic acidsInsulin sensitivityHigher insulin sensitivity indexPlasma epoxyeicosatrienoic acidsGlucose-stimulated insulin secretionBody mass indexArg/ArgSoluble epoxide hydrolase activitySoluble epoxide hydrolaseMetabolic syndromeMass indexDisposition indexInsulin resistanceHyperglycemic clampInsulin secretionSensitivity indexEpoxide hydrolase activityEPHX2Hydrolase activitySecretionPhenotyping studiesMetabolic phenotyping studiesEpoxide hydrolaseGenetic variantsGenetic 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
Characterization of Genome-Wide Association-Identified Variants for Atrial Fibrillation in African Americans
Delaney JT, Jeff JM, Brown NJ, Pretorius M, Okafor HE, Darbar D, Roden DM, Crawford DC. Characterization of Genome-Wide Association-Identified Variants for Atrial Fibrillation in African Americans. PLOS ONE 2012, 7: e32338. PMID: 22384221, PMCID: PMC3285683, DOI: 10.1371/journal.pone.0032338.Peer-Reviewed Original Research
2011
CYP4A11 variant is associated with high-density lipoprotein cholesterol in women
White CC, Feng Q, Cupples LA, Gainer JV, Dawson EP, Wilke RA, Brown NJ. CYP4A11 variant is associated with high-density lipoprotein cholesterol in women. The Pharmacogenomics Journal 2011, 13: 44-51. PMID: 21912424, PMCID: PMC3380161, DOI: 10.1038/tpj.2011.40.Peer-Reviewed Original ResearchConceptsHigh-density lipoprotein cholesterolFramingham Offspring StudyEpoxyeicosatrienoic acidsLipoprotein cholesterolLow HDLOffspring StudyHDL-C concentrationsCYP4A11 variantsMetabolic parametersPPARα activationEndogenous peroxisomeHDLBioVU cohortWomenReduced activityΩ-hydroxylaseCohortCYP4A11CholesterolPrevalenceGenotypesThe Fok1 vitamin D receptor gene polymorphism is associated with plasma renin activity in Caucasians
Vaidya A, Sun B, Forman JP, Hopkins PN, Brown NJ, Kolatkar NS, Williams GH, Williams JS. The Fok1 vitamin D receptor gene polymorphism is associated with plasma renin activity in Caucasians. Clinical Endocrinology 2011, 74: 783-790. PMID: 21521263, PMCID: PMC3089671, DOI: 10.1111/j.1365-2265.2011.03991.x.Peer-Reviewed Original ResearchConceptsPlasma renin activityVitamin D receptorLow plasma renin activityDietary sodium balanceRenin-angiotensin systemRenin activityFok1 polymorphismSodium balanceVitamin D receptor gene polymorphismsD receptor gene polymorphismsPopulation of hypertensivesReceptor gene polymorphismsFok1 genotypeHyperPATH cohortD deficiencyMultivariable analysisNormotensive individualsVitamin DRenin expressionVDR geneCardiovascular diseaseD receptorHuman studiesGene polymorphismsT allele
2010
The Relationship between Peroxisome Proliferator-Activated Receptor-γ and Renin: A Human Genetics Study
Underwood PC, Sun B, Williams JS, Pojoga LH, Chamarthi B, Lasky-Su J, Raby BA, Hopkins PN, Jeunemaitre X, Brown NJ, Adler GK, Williams GH. The Relationship between Peroxisome Proliferator-Activated Receptor-γ and Renin: A Human Genetics Study. The Journal Of Clinical Endocrinology & Metabolism 2010, 95: e75-e79. PMID: 20631015, PMCID: PMC2936061, DOI: 10.1210/jc.2010-0270.Peer-Reviewed Original ResearchConceptsPRA levelsPeroxisome proliferator-activated receptor gamma agonistPlasma renin activity levelsProliferator-activated receptor gamma agonistsVolume retentionAfrican-American hypertensivesHigh PRA levelsLow-salt dietRenin activity levelsAngiotensin II infusionMajor allele carriersSingle nucleotide polymorphismsC allele carrier statusReceptor gamma agonistsAllele carrier statusII infusionHypertensive participantsCombined P valueHuman hypertensionGamma agonistsNucleotide polymorphismsAllele carriersPPARgamma agonistsPPARgamma geneRenin
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 miceHypertensionThe 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 subjectsBradykinin 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
The 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 Americans
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 activityAn application of conditional logistic regression and multifactor dimensionality reduction for detecting gene-gene Interactions on risk of myocardial infarction: The importance of model validation
Coffey CS, Hebert PR, Ritchie MD, Krumholz HM, Gaziano JM, Ridker PM, Brown NJ, Vaughan DE, Moore JH. An application of conditional logistic regression and multifactor dimensionality reduction for detecting gene-gene Interactions on risk of myocardial infarction: The importance of model validation. BMC Bioinformatics 2004, 5: 49. PMID: 15119966, PMCID: PMC419697, DOI: 10.1186/1471-2105-5-49.Peer-Reviewed Original ResearchEnvironmentally determined genetic expression: clinical correlates with molecular variants of carbamyl phosphate synthetase I
Summar ML, Hall L, Christman B, Barr F, Smith H, Kallianpur A, Brown N, Yadav M, Willis A, Eeds A, Cermak E, Summar S, Wilson A, Arvin M, Putnam A, Wills M, Cunningham G. Environmentally determined genetic expression: clinical correlates with molecular variants of carbamyl phosphate synthetase I. Molecular Genetics And Metabolism 2004, 81: 12-19. PMID: 15050969, DOI: 10.1016/j.ymgme.2003.11.014.Peer-Reviewed Original ResearchRelationship 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
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