0000000000482141

AUTHOR

Manjinder S. Sandhu

showing 2 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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Large-scale association analysis identifies new risk loci for coronary artery disease

2016

Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r 2 < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes …

AdultAsian Continental Ancestry GroupMaleCandidate geneBIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICAPopulationEuropean Continental Ancestry GroupQuantitative Trait LociCADGenome-wide association studySingle-nucleotide polymorphismCoronary Artery Disease030204 cardiovascular system & hematologyBiologyQuantitative trait locusBioinformaticsPolymorphism Single NucleotideArticleWhite Peoplecoronary artery disease risk lociCell LineCoronary artery disease03 medical and health sciences0302 clinical medicineAsian PeopleRisk FactorsmedicineHumansgeneticsGene Regulatory NetworksGenetic Predisposition to Diseasecardiovascular diseasesPolymorphismeducation030304 developmental biologyGenetic associationAgedGenetics0303 health scienceseducation.field_of_studyAdult Aged Asian Continental Ancestry Group Cell Line Coronary Artery Disease; genetics European Continental Ancestry Group; genetics Female Gene Regulatory Networks Genetic Predisposition to Disease Genome-Wide Association Study Humans Male Middle Aged Polymorphism; Single Nucleotide Quantitative Trait Loci Risk FactorsSingle NucleotideMiddle Agedmedicine.disease3. Good healthFemaleGenome-Wide Association StudyNature Genetics
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