0000000000886635

AUTHOR

Ilaria Marini

showing 2 related works from this author

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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