0000000000459901

AUTHOR

Eric J.g. Sijbrands

0000-0001-8857-7389

showing 5 related works from this author

Identifying genetic risk variants for coronary heart disease in familial hypercholesterolemia: an extreme genetics approach

2015

Mutations in the low-density lipoprotein receptor (LDLR) gene cause familial hypercholesterolemia (FH), a disorder characterized by coronary heart disease (CHD) at young age. We aimed to apply an extreme sampling method to enhance the statistical power to identify novel genetic risk variants for CHD in individuals with FH. We selected cases and controls with an extreme contrast in CHD risk from 17 000 FH patients from the Netherlands, whose functional LDLR mutation was unequivocally established. The genome-wide association (GWA) study was performed on 249 very young FH cases with CHD and 217 old FH controls without CHD (above 65 years for males and 70 years of age for females) using the Ill…

AdultMaleRiskSettore MED/09 - Medicina InternaGenotypePopulationCoronary DiseaseSingle-nucleotide polymorphismGenome-wide association studyComorbidityFamilial hypercholesterolemiaQuantitative trait locusBiologymedicine.disease_causePolymorphism Single NucleotideArticleHyperlipoproteinemia Type IIYoung Adultsymbols.namesakeGene FrequencyRisk FactorsOdds RatioGeneticsmedicineHumansGenetic Predisposition to DiseaseeducationAllelesGenetics (clinical)AgedAged 80 and overGeneticsMutationeducation.field_of_studyfamilial hypercholesterolemiaPCSK9familial hypercholesterolemia; genetic risk factorgenetic risk factorGenetic VariationMiddle Agedmedicine.diseaseBonferroni correctionReceptors LDLCase-Control StudiesMutationsymbolsFemaleGenome-Wide Association StudyEuropean journal of human genetics
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Lomitapide affects HDL composition and function

2016

Abstract Background Lomitapide reduces low-density lipoprotein-cholesterol (LDL-C) but also high-density lipoprotein-cholesterol (HDL-C) levels. The latter may reduce the clinical efficacy of lomitapide. We investigated the effect of lomitapide on HDL-C levels and on cholesterol efflux capacity (CEC) of HDL in patients with homozygous familial hypercholesterolemia (HoFH). Methods and results Four HoFH patients were treated with increasing dosages of lomitapide. Lomitapide decreased LDL-C (range −34 to −89%). Total HDL-C levels decreased (range −16 to −34%) with a shift to buoyant HDL. ABCA1-mediated CEC decreased in all patients (range −39 to −99%). The changes of total, ABCG1- and SR-BI-me…

AdultMale0301 basic medicinemedicine.medical_specialtySettore MED/09 - Medicina InternaHDLHomozygous familial hypercholesterolemiaFamilial hypercholesterolemia030204 cardiovascular system & hematologyHyperlipoproteinemia Type IIYoung Adult03 medical and health scienceschemistry.chemical_compound0302 clinical medicineInternal medicineHumansMedicineIn patientClinical efficacyHyperlipoproteinemia Type IICholesterolbusiness.industryCholesterol HDLHomozygotenutritional and metabolic diseasesCholesterol LDLCholesterol efflux capacityAtherosclerosismedicine.diseaseCholesterol lowering drugsLomitapideLomitapideCholesterolPhenotypeTreatment Outcome030104 developmental biologyEndocrinologychemistryBenzimidazolesFemalelipids (amino acids peptides and proteins)Composition (visual arts)Cholesterol lowering drugHydroxymethylglutaryl-CoA Reductase InhibitorsLipoproteins HDLCardiology and Cardiovascular MedicinebusinessATP Binding Cassette Transporter 1Atherosclerosis
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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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Lomitapide treatment highly affects lipoprotein profile and HDL functionality in patients with familial hypercholesterolemia

2015

medicine.medical_specialtybusiness.industryFamilial hypercholesterolemiamedicine.diseaseLomitapidechemistry.chemical_compoundEndocrinologychemistryInternal medicinemedicineIn patientHdl functionalityCardiology and Cardiovascular MedicinebusinessLipoproteinAtherosclerosis
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Meta-Analysis of Genome-Wide Association Studies in >80 000 Subjects Identifies Multiple Loci for C-Reactive Protein Levels

2011

Background— C-reactive protein (CRP) is a heritable marker of chronic inflammation that is strongly associated with cardiovascular disease. We sought to identify genetic variants that are associated with CRP levels. Methods and Results— We performed a genome-wide association analysis of CRP in 66 185 participants from 15 population-based studies. We sought replication for the genome-wide significant and suggestive loci in a replication panel comprising 16 540 individuals from 10 independent studies. We found 18 genome-wide significant loci, and we provided evidence of replication for 8 of them. Our results confirm 7 previously known loci and introduce 11 novel loci that are implicated in p…

Netherlands Twin Register (NTR)Genome-wide association studyDisease030204 cardiovascular system & hematology0302 clinical medicineDESIGNRisk FactorsFRAMINGHAMNETHERLANDS TWIN REGISTERgeneticsCRP GENE2. Zero hungerGenetics0303 health scienceseducation.field_of_studybiologyCOMMON VARIANTS3. Good healthHNF1AC-Reactive Proteinmyocardial infarctionCardiovascular DiseasesMeta-analysis/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_beingCardiology and Cardiovascular MedicineVasculitisPopulationArticle03 medical and health sciencesINFLAMMATIONSDG 3 - Good Health and Well-beingPhysiology (medical)/dk/atira/pure/keywords/cohort_studies/netherlands_twin_register_ntr_medicineHumansGenetic Predisposition to DiseaseCORONARY-HEART-DISEASEALPHA-GENEeducation030304 developmental biologyGenetic associationEPIDEMIOLOGIC APPLICATIONSgenome-wide association studyC-reactive proteinmedicine.diseasemeta-analysisinflammationbiology.proteinGENETICALLY ISOLATED POPULATIONMetabolic syndromeBiomarkers
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