0000000000605948

AUTHOR

Tobias Balschun

showing 4 related works from this author

Mutational Characterization of the Bile Acid Receptor TGR5 in Primary Sclerosing Cholangitis

2010

Background: TGR5, the G protein-coupled bile acid receptor 1 (GPBAR1), has been linked to inflammatory pathways as well as bile homeostasis, and could therefore be involved in primary sclerosing cholangitis (PSC) a chronic inflammatory bile duct disease. We aimed to extensively investigate TGR5 sequence variation in PSC, as well as functionally characterize detected variants.Methodology/Principal Findings: Complete resequencing of TGR5 was performed in 267 PSC patients and 274 healthy controls. Six nonsynonymous mutations were identified in addition to 16 other novel single-nucleotide polymorphisms. To investigate the impact from the nonsynonymous variants on TGR5, we created a receptor mod…

Nonsynonymous substitutionMaleModels MolecularCandidate geneLinkage disequilibriumProtein ConformationDNA Mutational Analysislcsh:MedicineGenome-wide association studySUSCEPTIBILITYMULTIPLE SEQUENCE ALIGNMENTSReceptors G-Protein-CoupledMice0302 clinical medicineChildlcsh:ScienceGenetics and Genomics/Genetics of DiseaseGENE-EXPRESSIONGenetics0303 health sciencesMultidisciplinaryGastroenterology and Hepatology/Biliary TractCROHN-DISEASEMiddle AgedG protein-coupled bile acid receptor3. Good healthGenetics and Genomics/Gene FunctionULCERATIVE-COLITISChromosomes Human Pair 2WEB SERVER030211 gastroenterology & hepatologyFemaleResearch ArticleAdultAdolescentCholangitis SclerosingSingle-nucleotide polymorphismLocus (genetics)BiologyGenetics and Genomics/Complex TraitsPrimary sclerosing cholangitis03 medical and health sciencesYoung AdultDogsPROTEIN-COUPLED RECEPTORSLIVER-DISEASEmedicineAnimalsHumansAmino Acid SequenceBOWEL-DISEASE030304 developmental biologyAgedGastroenterology and Hepatology/Inflammatory Bowel DiseaseCYSTIC-FIBROSISlcsh:Rmedicine.diseaseGene Expression RegulationMutationCancer researchCattleColitis Ulcerativelcsh:Q
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Genome-Wide Association Analysis in Primary Sclerosing Cholangitis

2010

Background & Aims We aimed to characterize the genetic susceptibility to primary sclerosing cholangitis (PSC) by means of a genome-wide association analysis of single nucleotide polymorphism (SNP) markers. Methods A total of 443,816 SNPs on the Affymetrix SNP Array 5.0 (Affymetrix, Santa Clara, CA) were genotyped in 285 Norwegian PSC patients and 298 healthy controls. Associations detected in this discovery panel were re-examined in independent case-control panels from Scandinavia (137 PSC cases and 368 controls), Belgium/The Netherlands (229 PSC cases and 735 controls), and Germany (400 cases and 1832 controls). Results The strongest associations were detected near HLA-B at chromosome 6p21…

LOCIMacrophage Stimulating 1 (Hepatocyte Growth Factor-Like)Genome-wide association studySUSCEPTIBILITYGene FrequencyHLA AntigensRisk FactorsHEPATOCELLULAR-CARCINOMAOdds RatioBileBiliary TractINCREASED RISKOligonucleotide Array Sequence AnalysisGastroenterologyMULTIPLE-SCLEROSISCROHNS-DISEASEEuropePhenotypeULCERATIVE-COLITISInflammation MediatorsSNP arrayCholangitis SclerosingSingle-nucleotide polymorphismLocus (genetics)Human leukocyte antigenBiologyPolymorphism Single NucleotideRisk AssessmentCell LinePrimary sclerosing cholangitisGlypicansGenetic predispositionmedicineHumansGenetic Predisposition to DiseaseGene SilencingACID RECEPTOR TGR5Genetic associationInflammationChi-Square DistributionHepatologyGene Expression ProfilingGlypican 6medicine.diseaseGENEG-Protein-Coupled Bile Acid Receptor 1Case-Control StudiesImmunologyColitis UlcerativeGenome-Wide Association StudyINFLAMMATORY-BOWEL-DISEASEGastroenterology
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Genome-wide association analysis in primary sclerosing cholangitis identifies two non-HLA susceptibility loci

2011

Primary sclerosing cholangitis (PSC) is a chronic bile duct disease affecting 2.4-7.5% of individuals with inflammatory bowel disease. We performed a genome-wide association analysis of 2,466,182 SNPs in 715 individuals with PSC and 2,962 controls, followed by replication in 1,025 PSC cases and 2,174 controls. We detected non-HLA associations at rs3197999 in MST1 and rs6720394 near BCL2L11 (combined P = 1.1 x 10(-16) and P = 4.1 x 10(-8), respectively).

Cholangitis SclerosingPATHOGENESISSingle-nucleotide polymorphismGenome-wide association studyHuman leukocyte antigenBiologyInflammatory bowel diseasePolymorphism Single Nucleotidedigestive systemArticlePrimary sclerosing cholangitisPathogenesisCohort StudiesHLA AntigensProto-Oncogene ProteinsGeneticsmedicineHumansGenetic Predisposition to DiseaseBOWEL-DISEASEGenetic associationBcl-2-Like Protein 11Bile ductHepatocyte Growth FactorGene Expression Profilingdigestive oral and skin physiologyMembrane Proteinsmedicine.diseasedigestive system diseasesmedicine.anatomical_structureGenetic LociImmunologyApoptosis Regulatory ProteinsGenome-Wide Association Study
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Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci

2010

We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 x 10(-8)). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with gen…

Candidate geneGenetic LinkagePROTEINGenome-wide association studyInflammatory bowel diseaseGenomeACTIVATION0302 clinical medicineCrohn DiseaseSEQUENCE VARIANTSGenetics0303 health sciencesGenomeNEDD4 FAMILYCOMMON VARIANTSASSOCIATION3. Good health030220 oncology & carcinogenesis10076 Center for Integrative Human PhysiologyComputational Biology; Crohn Disease; Genetic Linkage; Genetic Loci; Genetic Variation; Genome Human; Humans; Reproducibility of Results; Genetic Predisposition to Disease; Genome-Wide Association Study; Geneticsinflammatory-bowel-disease sequence variants common variants nedd4 family association gene identification receptor protein activationHuman/dk/atira/pure/subjectarea/asjc/1300/1311Locus (genetics)610 Medicine & healthBiology03 medical and health sciences1311 GeneticsGenetic linkagemedicineGeneticsHumansGenetic Predisposition to Disease030304 developmental biologyGenetic associationIDENTIFICATIONRECEPTORComputational BiologyGenetic VariationReproducibility of Resultsmedicine.diseaseGENESettore MED/03 - Genetica Medica10199 Clinic for Clinical Pharmacology and ToxicologyGenetic Loci570 Life sciences; biologyHuman genomegenome-wide scan.meta-analysis.crohn's diseaseGenome-Wide Association StudyINFLAMMATORY-BOWEL-DISEASE
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