0000000000388387

AUTHOR

Oveis Jamialahmadi

showing 7 related works from this author

Exome-Wide Association Study on Alanine Aminotransferase Identifies Sequence Variants in the GPAM and APOE Associated With Fatty Liver Disease.

2021

BACKGROUND & AIMS: Fatty liver disease (FLD) is a growing epidemic that is expected to be the leading cause of end-stage liver disease within the next decade. Both environmental and genetic factors contribute to the susceptibility of FLD. Several genetic variants contributing to FLD have been identified in exome-wide association studies. However, there is still a missing hereditability indicating that other genetic variants are yet to be discovered. METHODS: To find genes involved in FLD, we first examined the association of missense and nonsense variants with alanine amino transferase at an exome-wide level in 425,671 participants from the UK Biobank. We then validated genetic variants wit…

0301 basic medicineGenome-wide association studyLiver disease0302 clinical medicineENRICHMENT ANALYSISNon-alcoholic Fatty Liver DiseaseRisk FactorsNonalcoholic fatty liver diseaseExomeCONFERS SUSCEPTIBILITYGeneticsINSULIN-RESISTANCEmedicine.diagnostic_testFatty liverGastroenterologyAlanine Transaminase1-Acylglycerol-3-Phosphate O-Acyltransferase3. Good healthGENOMEEuropePhenotypeLiver biopsy030211 gastroenterology & hepatologyNonalcoholic Fatty Liver DiseaseMAFLDSingle-nucleotide polymorphismBiologyTransaminaseRisk Assessment03 medical and health sciencesApolipoproteins ENAFLDmedicineGenetic predispositionHumansGenetic Predisposition to DiseaseHEPATIC STEATOSISGenetic associationMAFLD Phenotype Reproducibility of Results Risk Assessment Risk Factors Transcriptome Genetic Variation Metabolic Associated Fatty Liver Disease Nonalcoholic Fatty Liver Disease Transaminase 1-Acylglycerol-3-Phosphate O-Acyltransferase Alanine Transaminase Apolipoproteins E Biomarkers Europe Exome Gene Expression Profiling Genetic Predisposition to Disease Genome-Wide Association Study Humans Non-alcoholic Fatty Liver DiseaseHepatologyMUTATIONSGene Expression ProfilingGenetic VariationReproducibility of Resultsmedicine.diseaseX-RECEPTORGENE030104 developmental biology3121 General medicine internal medicine and other clinical medicineMetabolic Associated Fatty Liver DiseaseRNA-SEQ DATATranscriptomePATHOGENICITYBiomarkersGenome-Wide Association StudyGastroenterology
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Non-invasive stratification of hepatocellular carcinoma risk in non-alcoholic fatty liver using polygenic risk scores

2021

Background & Aims: Hepatocellular carcinoma (HCC) risk stratification in individuals with dysmetabolism is a major unmet need. Genetic predisposition contributes to non-alcoholic fatty liver disease (NAFLD). We aimed to exploit robust polygenic risk scores (PRS) that can be evaluated in the clinic to gain insight into the causal relationship between NAFLD and HCC, and to improve HCC risk stratification. Methods: We examined at-risk individuals (NAFLD cohort, n = 2,566; 226 with HCC; and a replication cohort of 427 German patients with NAFLD) and the general population (UK Biobank [UKBB] cohort, n = 364,048; 202 with HCC). Variants in PNPLA3-TM6SF2-GCKR-MBOAT7 were combined in a hepatic …

0301 basic medicineOncologyLiver CirrhosisMaleMultifactorial InheritanceCirrhosis0302 clinical medicineRisk FactorsNon-alcoholic Fatty Liver DiseaseHepatic fatAdiposityeducation.field_of_studyFatty liverLiver NeoplasmsMiddle AgedPrognosisEuropeCirrhosisLiverCohort030211 gastroenterology & hepatologyBiomarker; Cirrhosis; Genetics; Hepatic fat; Non-alcoholic fatty liver diseaseFemaleLiver cancerCohort studymedicine.medical_specialtyCarcinoma HepatocellularSettore MED/12 - GASTROENTEROLOGIAPopulationRisk Assessment03 medical and health sciencesBiomarker Cirrhosis Genetics Hepatic fat Non-alcoholic fatty liver disease Cross-Sectional Studies Europe Female Genetic Predisposition to Disease Humans Liver Liver Cirrhosis Male Mediation Analysis Middle Aged Multifactorial Inheritance Predictive Value of Tests Prognosis Risk Assessment Risk Factors Adiposity Carcinoma Hepatocellular Non-alcoholic Fatty Liver DiseaseGeneticPredictive Value of TestsInternal medicinemedicineGenetic predispositionGeneticsHumansGenetic Predisposition to DiseaseeducationCirrhosiMediation AnalysisHepatologybusiness.industryCarcinomaCase-control studyHepatocellularBiomarkermedicine.diseasedigestive system diseases030104 developmental biologyCross-Sectional StudiesbusinessJournal of Hepatology
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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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Macrophage scavenger receptor 1 mediates lipid-induced inflammation in non-alcoholic fatty liver disease.

2022

Background & Aims: Obesity-associated inflammation is a key player in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, the role of macrophage scavenger receptor 1 (MSR1, CD204) remains incompletely understood. Methods: A total of 170 NAFLD liver biopsies were processed for transcriptomic analysis and correlated with clinicopathological features. Msr1(-/-) and wild-type mice were subjected to a 16-week high-fat and high-cholesterol diet. Mice and ex vivo human liver slices were treated with a monoclonal antibody against MSR1. Genetic susceptibility was assessed using genome-wide association study data from 1,483 patients with NAFLD and 430,101 participants of the U…

immunometabolism610 Medicine & healthGastroenterology and HepatologyInbred C57BLDiet High-FatAntibodiesSTEATOHEPATITIS03 medical and health sciencesMice0302 clinical medicineNon-alcoholic Fatty Liver DiseaseMonoclonalGastroenterologiAnimalsHumansObesity610 Medicine & health030304 developmental biologyInflammation0303 health sciencesScience & Technologyimmunometabolism; inflammation; macrophages; NASH; Animals; Antibodies Monoclonal; Diet High-Fat; Genome-Wide Association Study; Humans; Inflammation; Lipids; Liver; Mice; Mice Inbred C57BL; Obesity; Non-alcoholic Fatty Liver DiseaseGastroenterology & HepatologyHepatologyNASHNASH immunometabolism inflammation macrophagesAntibodies MonoclonalLipids3. Good healthmacrophagesDietALPHAMice Inbred C57BLHigh-Fatmacrophages; immunometabolism; NASH; inflammationLiverinflammation3121 General medicine internal medicine and other clinical medicine030211 gastroenterology & hepatologyHuman medicineLife Sciences & BiomedicineGenome-Wide Association StudyJournal of hepatology
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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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Rare ATG7 genetic variants predispose patients to severe fatty liver disease

2022

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disorders and has a strong heritable component. The aim of this study was to identify new loci that contribute to severe NAFLD by examining rare variants.Methods: We performed whole-exome sequencing in in-dividuals with NAFLD and advanced fibrosis or hepatocellular carcinoma (n = 301) and examined the enrichment of likely pathogenic rare variants vs. the general population. This was followed by validation at the gene level.Results: In patients with severe NAFLD, we observed an enrichment of the p.P426L variant (rs143545741 C>T; odds ratio [OR] 5.26, 95% CI 2.1-12.6; p = 0.003) of autophagy-rela…

InflammationLiver CirrhosisautophagyHepatologyBiopsyNAFLD NASH autophagy genetics liver fibrosisCarcinomaLiver NeoplasmsNASHHepatocellularAutophagy-Related Protein 7NAFLD; NASH; autophagy; genetics; liver fibrosis; Autophagy-Related Protein 7; Biopsy; Humans; Inflammation; Liver; Liver Cirrhosis; Carcinoma Hepatocellular; Liver Neoplasms; Non-alcoholic Fatty Liver DiseaseLiverNon-alcoholic Fatty Liver DiseaseNAFLDHumansgeneticsgeneticautophagy; genetics; liver fibrosis; NAFLD; NASHliver fibrosis
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Macrophage Scavenger Receptor 1 mediates lipid-induced inflammation in non-alcoholic fatty liver disease

2020

AbstractObesity-associated inflammation is a key player in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, the exact mechanisms remain incompletely understood. Here we demonstrate that macrophage scavenger receptor 1 (MSR1, CD204) expression is associated with the occurrence of hepatic lipid-laden foamy macrophages and correlates with the degree of steatosis and steatohepatitis in a cohort of 170 NAFLD patients. Mice lacking Msr1 are protected against high fat-cholesterol diet (HFD)-induced metabolic disorder, showing fewer hepatic lipid-laden foamy macrophages, less hepatic inflammation, improved dyslipidemia and glucose tolerance, while showing a change in hepatic …

0303 health sciencesmedicine.medical_specialtyLipopolysaccharidebusiness.industryFatty liverInflammationmedicine.disease3. Good healthMSR1Pathogenesis03 medical and health scienceschemistry.chemical_compound0302 clinical medicineEndocrinologychemistryFibrosisInternal medicineMedicine030211 gastroenterology & hepatologySteatohepatitismedicine.symptomSteatosisbusiness030304 developmental biology
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