0000000000482121

AUTHOR

Wiek H. Van Gilst

showing 4 related works from this author

Separating the Mechanism-Based and Off-Target Actions of Cholesteryl Ester Transfer Protein Inhibitors With CETP Gene Polymorphisms

2010

Background— Cholesteryl ester transfer protein (CETP) inhibitors raise high-density lipoprotein (HDL) cholesterol, but torcetrapib, the first-in-class inhibitor tested in a large outcome trial, caused an unexpected blood pressure elevation and increased cardiovascular events. Whether the hypertensive effect resulted from CETP inhibition or an off-target action of torcetrapib has been debated. We hypothesized that common single-nucleotide polymorphisms in the CETP gene could help distinguish mechanism-based from off-target actions of CETP inhibitors to inform on the validity of CETP as a therapeutic target. Methods and Results— We compared the effect of CETP single-nucleotide polymorphisms …

high-density lipoproteinsEpidemiologyBLOOD-PRESSUREPharmacologyDISEASEchemistry.chemical_compoundDOUBLE-BLINDHigh-density lipoprotein:CIENCIAS MÉDICAS ::Medicina interna [UNESCO]Polymorphism (computer science)Physiology (medical)Cholesterylester transfer proteinGeneticsMedicinegeneticsHigh-density lipoproteinsGENOME-WIDE ASSOCIATIONUNESCO::CIENCIAS MÉDICAS ::Medicina internaPharmacologyHDL CHOLESTEROLbiologybusiness.industryCholesterolTorcetrapib:CIENCIAS MÉDICAS [UNESCO]Genetics ; Pharmacology ; Epidemiology ; High-density lipoproteinsDose–response relationshipBlood pressurechemistryATHEROSCLEROSISUNESCO::CIENCIAS MÉDICASbiology.proteinMENDELIAN RANDOMIZATIONepidemiology; genetics; high-density lipoproteins; pharmacologylipids (amino acids peptides and proteins)epidemiologyTORCETRAPIBpharmacologyCardiology and Cardiovascular MedicinebusinessHIGH-DENSITY-LIPOPROTEINLIPID-LEVELSLipoproteinCirculation
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Genome-wide association analyses identify 18 new loci associated with serum urate concentrations

2013

Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional…

Candidate geneInhibins/geneticsGenome-wide association studyGENETIC-LOCIchemistry.chemical_compound0302 clinical medicineserum urateGene FrequencyGout/bloodassociation analysis serum urateGlucose/metabolismSettore MED/14 - NEFROLOGIAHyperuricemiaserum; urate; genePOPULATIONMETABOLIC SYNDROMEGenetics0303 health scienceseducation.field_of_studybiologyPolymorphism Single Nucleotide/genetics3. Good healthHYPERURICEMIAGenetic Loci/genetics/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_beingSLC22A12Single Nucleotide/geneticsSNPsSignal TransductionMOLECULAR PHYSIOLOGYserum urate concentrations gout genome-wide meta-analysisEuropean Continental Ancestry GroupPopulationPolymorphism Single NucleotideWhite PeopleUric Acid/bloodserum urate concentrationsgenome-wide meta-analysis03 medical and health sciencesSDG 3 - Good Health and Well-beinguric acidGeneticsmedicineHumansInhibinsPolymorphismeducation030304 developmental biology030203 arthritis & rheumatologyAnalysis of VarianceGOUTIDENTIFICATIONTRANSPORTERCARDIOVASCULAR-DISEASE RISKta3121medicine.diseaseassociation analysisGoutmeta-analysisGlucosechemistryGenetic Locigenome-wide association studiesbiology.proteinSignal Transduction/geneticsUric acidURIC-ACID LEVELSGenome-Wide Association StudySLC2A9
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Association Between Chromosome 9p21 Variants and the Ankle-Brachial Index Identified by a Meta-Analysis of 21 Genome-Wide Association Studies

2012

Background— Genetic determinants of peripheral arterial disease (PAD) remain largely unknown. To identify genetic variants associated with the ankle-brachial index (ABI), a noninvasive measure of PAD, we conducted a meta-analysis of genome-wide association study data from 21 population-based cohorts. Methods and Results— Continuous ABI and PAD (ABI ≤0.9) phenotypes adjusted for age and sex were examined. Each study conducted genotyping and imputed data to the ≈2.5 million single nucleotide polymorphisms (SNPs) in HapMap. Linear and logistic regression models were used to test each SNP for association with ABI and PAD using additive genetic models. Study-specific data were combined using fi…

Malegenetic associationGenome-wide association studyAetiology screening and detection [ONCOL 5]030204 cardiovascular system & hematologyBioinformaticsCohort Studies0302 clinical medicineRisk FactorsGenotypeCARDIOVASCULAR RISK-FACTORSInternational HapMap ProjectGenetics (clinical)POPULATIONGeneticsAged 80 and overPeripheral Vascular Diseases0303 health scienceseducation.field_of_studyAge FactorsMiddle AgedPhenotypeperipheral vascular diseaseMeta-analysiscardiovascular system/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_beingCORONARY-ARTERY-DISEASEFemaleCardiology and Cardiovascular MedicineChromosomes Human Pair 9AdultSUSCEPTIBILITY LOCIGenotypePopulationHapMap ProjectBiologyPolymorphism Single NucleotideArticleMolecular epidemiology [NCEBP 1]03 medical and health sciencesSex FactorsSDG 3 - Good Health and Well-beingGeneticscohort studyHumansAnkle Brachial Indexcardiovascular diseasesAlleleeducationHealth aging / healthy living Cardiovascular diseases [IGMD 5]AllelesMolecular epidemiology Aetiology screening and detection [NCEBP 1]030304 developmental biologyGenetic associationAgedCyclin-Dependent Kinase Inhibitor p15ABDOMINAL AORTIC-ANEURYSMcohort study ; genetic association ; genome-wide association study ; meta-analysis ; peripheral vascular diseasegenome-wide association studyMORTALITYChromosomeGENEmeta-analysisbody regionsLogistic ModelsMYOCARDIAL-INFARCTIONATHEROSCLEROSISSEQUENCE VARIANThuman activities
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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

2016

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation o…

0301 basic medicineNephrologyGenetics and Molecular Biology (all)estimated glomerular filtration rateestimated glomerular filtration rate chronic kidney disease genetic determinantsGeneral Physics and AstronomyKidney developmentGenome-wide association studyBiochemistrySettore MED/14 - NEFROLOGIARenal InsufficiencyChronicGeneticsAGEN Consortiumddc:616education.field_of_studyKidneyStage renal-diseaseMultidisciplinaryGenome-wide associationCHARGe-Heart Failure GroupGene Expression Regulation; Genome-Wide Association Study; Genotype; Humans; Renal Insufficiency Chronic; Genetic Predisposition to Disease; Biochemistry Genetics and Molecular Biology (all); Chemistry (all); Physics and Astronomy (all)QChemistry (all)MetaanalysisGene Expression Regulation; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Humans; Renal Insufficiency Chronic/geneticsBiological sciencesSerum creatininemedicine.anatomical_structureEfficientRonyons -- FisiologiaHypertensionICBP ConsortiumTransmembrane transporter activitygenetic association loci kidney functionCARDIOGRAMHumanmedicine.medical_specialtyGenotypeSciencePopulationRenal functionECHOGen ConsortiumReplicationBiologyEnvironmentResearch SupportGeneral Biochemistry Genetics and Molecular BiologyN.I.H.genetic determinants03 medical and health sciencesPhysics and Astronomy (all)GENOME-WIDE ASSOCIATION ; FALSE DISCOVERY RATES ; STAGE RENAL-DISEASE ; SERUM CREATININE ; METAANALYSIS ; VARIANTS ; INDIVIDUALS ; POPULATION ; RISK ; HYPERTENSIONKidney functionResearch Support N.I.H. ExtramuralInternal medicineMD MultidisciplinarymedicineGeneticsJournal ArticleHumanseGFRcrea; eGFRcysGenetic Predisposition to Diseaseddc:610GenetikRenal Insufficiency ChronicMortalityeducationddc:613Biochemistry Genetics and Molecular Biology (all)urogenital systemIndividualsExtramuralGeneral Chemistryta3121medicine.diseaseR1030104 developmental biologyGene Expression RegulationBiochemistry Genetics and Molecular Biology (all); Chemistry (all); Physics and Astronomy (all)570 Life sciences; biologyGenèticachronic kidney diseaseKidney diseaseGenome-Wide Association StudyMeta-Analysis
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