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 polymorphismHypertensionCYP4A11 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-hydroxylaseCohortCYP4A11CholesterolPrevalenceGenotypes
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
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 variantsAla92 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
2000
Angiotensin-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
1996
Angiotensin converting enzyme gene polymorphism: Potential silencer motif and impact on progression in IgA nephropathy
Hunley T, Julian B, Phillips J, Summar M, Yoshida H, Horn R, Brown N, Fogo A, Ichikawa I, Kon V. Angiotensin converting enzyme gene polymorphism: Potential silencer motif and impact on progression in IgA nephropathy. Kidney International 1996, 49: 571-577. PMID: 8821846, DOI: 10.1038/ki.1996.81.Peer-Reviewed Original ResearchConceptsRenin-angiotensin systemIgA nephropathyRenal functionDD genotypeMyocardial infarctionCardiovascular diseaseACE genotype frequenciesGene polymorphismsBiopsy-proven IgA nephropathyACE I/D polymorphismAGT 235TEnzyme deletion polymorphismNormal serum creatinineRenal disease progressionACE DD genotypeEnzyme gene polymorphismGenotype frequenciesI gene polymorphismStable creatinineAngiotensin systemSerum creatinineRenal statusVentricular hypertrophyCaucasian patientsRisk factors