0000000000417654

AUTHOR

Vesa Kärjä

showing 5 related works from this author

The MBOAT7-TMC4 Variant rs641738 Increases Risk of Nonalcoholic Fatty Liver Disease in Individuals of European Descent

2016

Background & Aims Nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver damage and is characterized by steatosis. Genetic factors increase risk for progressive NAFLD. A genome-wide association study showed that the rs641738 C>T variant in the locus that contains the membrane bound O-acyltransferase domain-containing 7 gene (MBOAT7, also called LPIAT1) and transmembrane channel-like 4 gene (TMC4) increased the risk for cirrhosis in alcohol abusers. We investigated whether the MBOAT7-TMC4 is a susceptibility locus for the development and progression of NAFLD. Methods We genotyped rs641738 in DNA collected from 3854 participants from the Dallas Heart Study (a multi-ethnic…

Liver CirrhosisMale0301 basic medicineCirrhosisBiopsyProton Magnetic Resonance SpectroscopyPhosphatidylinositolsTriglycerideSeverity of Illness IndexGastroenterologyLiver disease0302 clinical medicineNon-alcoholic Fatty Liver DiseaseRisk FactorsNonalcoholic fatty liver diseaseMembrane Proteineducation.field_of_studyArachidonic Acidmedicine.diagnostic_testNASHGastroenterologyTexasEuropePhenotypeLiverLiver biopsyFemale030211 gastroenterology & hepatologyTexaCase-Control StudiePhosphatidylinositolHumanmedicine.medical_specialtyAcyltransferaseLiver CirrhosiEuropean Continental Ancestry GroupPopulationTM6SF2White PeopleArticle03 medical and health sciencesArachidonic Acid; NASH; PNPLA3; TM6SF2; Acetyltransferases; Acyltransferases; Biopsy; Case-Control Studies; Cross-Sectional Studies; Europe; European Continental Ancestry Group; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Liver; Liver Cirrhosis; Male; Membrane Proteins; Non-alcoholic Fatty Liver Disease; Phenotype; Phosphatidylinositols; Proton Magnetic Resonance Spectroscopy; Risk Factors; Severity of Illness Index; Texas; Triglycerides; Polymorphism GeneticGeneticAcetyltransferasesInternal medicineAcetyltransferasemedicineHumansGenetic Predisposition to DiseasePolymorphismeducationPNPLA3TriglyceridesCross-Sectional StudiePolymorphism GeneticHepatologybusiness.industryRisk FactorCase-control studyMembrane Proteinsmedicine.diseaseCross-Sectional Studies030104 developmental biologyEndocrinologyCase-Control StudiesSteatosisbusinessAcyltransferasesGenome-Wide Association StudyTM6SF2Gastroenterology
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Programmed cell death 1 genetic variant and liver damage in nonalcoholic fatty liver disease

2023

Background and aims: Programmed cell death 1/programmed cell death-ligand 1 (PD-1/PDL-1) axis has been reported to modulate liver inflammation and progression to hepatocellular carcinoma (HCC) in patients with nonalcoholic fatty liver disease (NAFLD). Here, we examined whether the PDCD1 variation is associated with NAFLD severity in individuals with liver biopsy. Methods: We examined the impact of PDCD1 gene variants on HCC, as robust severe liver disease phenotype in UK Biobank participants. The strongest genetic association with the rs13023138 G>C variation was subsequently tested for association with liver damage in 2889 individuals who underwent liver biopsy for suspected nonalcoholi…

Settore MED/12 - GastroenterologiaHepatologySettore BIO/13 - Biologia ApplicataGastroenterologyCXCR6 NAFLD NASH PDCD1 checkpoint inhibitorsDigestive and Liver Disease
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Statin use and non-alcoholic steatohepatitis in at risk individuals.

2015

Background & Aims Excess hepatic free cholesterol contributes to the pathogenesis of non-alcoholic steatohepatitis, and statins reduce cholesterol synthesis. Aim of this study was to assess whether statin use is associated with histological liver damage related to steatohepatitis. Methods The relationship between statin use, genetic risk factors, and liver damage was assessed in a multi-center cohort of 1201 European individuals, who underwent liver biopsy for suspected non-alcoholic steatohepatitis. Results Statin use was recorded in 107 subjects, and was associated with protection from steatosis, NASH, and fibrosis stage F2-F4, in a dose-dependent manner (adjusted p <0.05 for all).…

AdultMaleRiskmedicine.medical_specialtyStatinmedicine.drug_classBiopsyGastroenterologyNon-alcoholic Fatty Liver DiseaseInternal medicinemedicineHumansSteatosiPNPLA3AgedHepatologymedicine.diagnostic_testbusiness.industryNASHStatinMembrane ProteinsLipaseHepatologyMiddle AgedImpaired fasting glucosemedicine.diseaseCholesterolEndocrinologyLogistic ModelsLiverLiver biopsyCohortFemaleSteatosisSteatohepatitisHydroxymethylglutaryl-CoA Reductase InhibitorsbusinessNon-alcoholic steatohepatitiTM6SF2Journal of hepatology
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Transmembrane 6 Superfamily Member 2 Gene Variant Disentangles Nonalcoholic Steatohepatitis From Cardiovascular Disease

2015

Excess hepatic storage of triglycerides is considered a benign condition, but nonalcoholic steatohepatitis (NASH) may progress to fibrosis and promote atherosclerosis. Carriers of the TM6SF2 E167K variant have fatty liver as a result of reduced secretion of very-low-density lipoproteins (VLDLs). As a result, they have lower circulating lipids and reduced risk of myocardial infarction. In this study, we aimed to assess whether TM6SF2 E167K affects liver damage and cardiovascular outcomes in subjects at risk of NASH. Liver damage was evaluated in 1,201 patients who underwent liver biopsy for suspected NASH; 427 were evaluated for carotid atherosclerosis. Cardiovascular outcomes were assessed …

medicine.medical_specialtyHepatologymedicine.diagnostic_testbusiness.industryFatty liverOdds ratioHepatologymedicine.diseaseLower riskEndocrinologyInternal medicineLiver biopsyCohortmedicineSteatosisNASH TM6SF2businessTM6SF2
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PSD3 downregulation confers protection against fatty liver disease

2022

Fatty liver disease (FLD) is a growing health issue with burdening unmet clinical needs. FLD has a genetic component but, despite the common variants already identified, there is still a missing heritability component. Using a candidate gene approach, we identify a locus (rs71519934) at the Pleckstrin and Sec7 domain-containing 3 (PSD3) gene resulting in a leucine to threonine substitution at position 186 of the protein (L186T) that reduces susceptibility to the entire spectrum of FLD in individuals at risk. PSD3 downregulation by short interfering RNA reduces intracellular lipid content in primary human hepatocytes cultured in two and three dimensions, and in human and rodent hepatoma cell…

GenotypeEndocrinology Diabetes and MetabolismVARIANTSUSCEPTIBILITYPolymorphism Single NucleotideArticleCell LineMiceRibonucleasesPhysiology (medical)Internal MedicineAnimalsGuanine Nucleotide Exchange FactorsHumansRNA-SeqAllelesNon-alcoholic steatohepatitisNONALCOHOLIC STEATOHEPATITISHERITABILITYGene Expression ProfilingfungiNASHGenetic VariationCell BiologyMetabolic syndromeFatty LiverMetabolismGene Expression RegulationLiverEXOME-WIDE ASSOCIATION3121 General medicine internal medicine and other clinical medicineACIDHepatocytesSECRETIONDisease SusceptibilityVLDLBiomarkersTRIGLYCERIDESNon-alcoholic fatty liver disease
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