0000000000160701

AUTHOR

Ester Ciociola

showing 5 related works from this author

Rare <i>Atg7</i> Genetic Variants Predispose to Severe Fatty Liver Disease

2021

Background&Aims: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease and has a strong heritable component. The aim of this study was to identify new genes involved in NAFLD pathogenesis. Methods: We examined rare variants captured by whole-exome sequencing in individuals with severe fibrosis or hepatocellular carcinoma due to NAFLD (severe NAFLD, n=301) after variant prioritization.  We replicated the results in the UK Biobank and the Liver biopsy cohort (n=2268). Results: We observed an enrichment of the p.P426L variant (rs143545741 C>T; OR=7.2, 2.3-17.3; p C; MAF=0.060 vs. 0.035; OR=1.7, 1.2-2.5; p=0.003). In the UK Biobank cohort, the p.V471A variant wa…

medicine.medical_specialtymedicine.diagnostic_testbusiness.industryFatty livermedicine.diseaseChronic liver diseaseGastroenterologyPathogenesisLiver diseaseBallooning degenerationLiver biopsyInternal medicineHepatocellular carcinomamedicineSteatosisbusinessSSRN Electronic Journal
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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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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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CLINICAL CHARACTERISTICS AND PLASMA LIPIDS IN SUBJECTS WITH FAMILIAL COMBINED HYPOLIPIDEMIA: A POOLED ANALYSIS

2013

Background. Angiopoietin-like 3 (ANGPTL3) regulates lipoprotein metabolism by modulating extracellular lipases. Loss-of function mutations in ANGPTL3 gene cause familial combined hypolipidemia (FHBL2). The mode of inheritance and hepatic and vascular consequences of FHBL2 have not been fully elucidated. To get further insights on these aspects, we re-evaluated the clinical and the biochemical characteristics of all reported cases of FHBL2. Methods and Results. One hundred fteen FHBL2 individuals carrying 13 different mutations in the ANGPTL3 gene (14 homozygotes, 8 compound heterozygotes and 93 heterozygotes) and 402 controls were considered. Carriers of 2 mutant alleles had undetectable pl…

ANGPTL3 mutations; angiopoietin-like 3; cardiovascular disease; diabetes mellitus; fatty liverSettore MED/09 - Medicina InternaCompound heterozygosityBiochemistryCohort StudiesHypobetalipoproteinemiasEndocrinologyANGPTL3cardiovascular diseaseGenotypeChildLipoproteinclinical characteristicsAged 80 and overbiologydiabetes mellituFatty liverHomozygoteLipoprotein(a)Middle AgedANGPTL3 mutationLipidsCardiovascular Diseasesdiabetes mellitusANGPTL3 Familial combined hypolipidemia LipoproteinAdultmedicine.medical_specialtyHeterozygoteANGPTL3; Familial combined hypolipidemia; clinical characteristicsAdolescentEvinacumabQD415-436Young AdultDiabetes mellitusInternal medicinemedicineHumansANGPTL3 mutationsAlleleFamilial combined hypolipidemiaAgedAngiopoietin-Like Protein 3fatty liverangiopoietin-like 3Cell Biologymedicine.diseaseEndocrinologyAngiopoietin-like ProteinsGene Expression RegulationMutationbiology.proteinPatient-Oriented and Epidemiological ResearchAngiopoietinsLipoproteinLipoprotein(a)
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