0000000000367149

AUTHOR

Alessandro Pietrelli

showing 3 related works from this author

Telomerase reverse transcriptase germline mutations and hepatocellular carcinoma in patients with nonalcoholic fatty liver disease

2017

Abstract In an increasing proportion of cases, hepatocellular carcinoma (HCC) develops in patients with nonalcoholic fatty liver disease (NAFLD). Mutations in telomerase reverse transcriptase (hTERT) are associated with familial liver diseases. The aim of this study was to examine telomere length and germline hTERT mutations as associated with NAFLD‐HCC. In 40 patients with NAFLD‐HCC, 45 with NAFLD‐cirrhosis and 64 healthy controls, peripheral blood telomere length was evaluated by qRT‐PCR and hTERT coding regions and intron–exon boundaries sequenced. We further analyzed 78 patients affected by primary liver cancer (NAFLD‐PLC, 76 with HCC). Enrichment of rare coding mutations (allelic frequ…

MaleCancer ResearchHepatocellular carcinomaSeverity of Illness IndexGermlineLoss of heterozygosityCohort StudiesLiver disease0302 clinical medicineNon-alcoholic Fatty Liver DiseaseNuclear Medicine and ImagingNonalcoholic fatty liver disease80 and overLeukocytesTelomeraseTelomere ShorteningOriginal ResearchCancer BiologyAged 80 and overHepatocellular carcinoma; Nonalcoholic fatty liver; Rare germline mutations; Telomerase reverse transcriptase; Telomere; Oncology; Radiology Nuclear Medicine and Imaging; Cancer ResearchtelomereLiver Neoplasmstelomerase reverse transcriptaseMiddle Aged3. Good healthPhenotypeOncology030220 oncology & carcinogenesisHepatocellular carcinoma030211 gastroenterology & hepatologyFemaleDisease SusceptibilityRadiologySequence AnalysisRare germline mutationCarcinoma HepatocellularMononuclearBiology03 medical and health sciencesGermline mutationHepatocellular carcinoma; Nonalcoholic fatty liver; Rare germline mutations; Telomerase reverse transcriptase; Telomere; Aged; Aged 80 and over; Alleles; Amino Acid Substitution; Carcinoma Hepatocellular; Cohort Studies; Computational Biology; Disease Susceptibility; Female; Genetic Association Studies; Humans; Leukocytes Mononuclear; Liver Neoplasms; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Phenotype; Sequence Analysis DNA; Severity of Illness Index; Telomerase; Telomere; Telomere Shortening; Germ-Line Mutationmedicinenonalcoholic fatty liverHumansRadiology Nuclear Medicine and imagingTelomerase reverse transcriptaseAllelesGenetic Association StudiesGerm-Line MutationAgedrare germline mutationsCarcinomaComputational BiologyHepatocellularDNASequence Analysis DNAmedicine.diseasedigestive system diseasesTelomereAmino Acid SubstitutionCancer researchLeukocytes MononuclearCancer Medicine
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Rare Pathogenic Variants Predispose to Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease

2019

AbstractNonalcoholic fatty liver disease (NAFLD) is a rising cause of hepatocellular carcinoma (HCC). We examined whether inherited pathogenic variants in candidate genes (n = 181) were enriched in patients with NAFLD-HCC. To this end, we resequenced peripheral blood DNA of 142 NAFLD-HCC, 59 NAFLD with advanced fibrosis, and 50 controls, and considered 404 healthy individuals from 1000 G. Pathogenic variants were defined according to ClinVar, likely pathogenic as rare variants predicted to alter protein activity. In NAFLD-HCC patients, we detected an enrichment in pathogenic (p = 0.024), and likely pathogenic variants (p = 1.9*10−6), particularly in APOB (p = 0.047). APOB variants were asso…

0301 basic medicineMaleCandidate geneApolipoprotein Blcsh:MedicineGastroenterologyLiver diseasechemistry.chemical_compound0302 clinical medicineNon-alcoholic Fatty Liver DiseaseRisk FactorsNonalcoholic fatty liver diseaseSequestosome-1 ProteinGenetic riskHCClcsh:ScienceMultidisciplinarybiologyLiver NeoplasmsMiddle Aged3. Good healthCholesterolHepatocellular carcinomaApolipoprotein B-100FemaleAged; Apolipoprotein B-100; Carcinoma Hepatocellular; Case-Control Studies; Cholesterol HDL; Female; Genetic Predisposition to Disease; Glial Cell Line-Derived Neurotrophic Factor Receptors; Humans; Liver Neoplasms; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Reproducibility of Results; Risk Factors; Sequestosome-1 Proteinmedicine.medical_specialtyCarcinoma HepatocellularGlial Cell Line-Derived Neurotrophic Factor ReceptorsHDLSettore BIO/18 - GENETICAdigestive systemArticle03 medical and health sciencesInternal medicinemedicineHumansGenetic Predisposition to DiseaseGeneAgedCholesterolbusiness.industrylcsh:RCarcinomaCholesterol HDLnutritional and metabolic diseasesReproducibility of ResultsHepatocellularmedicine.diseasedigestive system diseases030104 developmental biologychemistryNASH HCCCase-Control Studiesbiology.proteinlcsh:Qgeneticbusiness030217 neurology & neurosurgery
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The rs2294918 E434K variant modulates patatin-like phospholipase domain-containing 3 expression and liver damage

2016

The patatin-like phosholipase domain-containing 3 (PNPLA3) rs738409 polymorphism (I148M) is a major determinant of hepatic fat and predisposes to the full spectrum of liver damage in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate whether additional PNPLA3 coding variants contribute to NAFLD susceptibility, first in individuals with contrasting phenotypes (with early-onset NAFLD vs. very low aminotransferases) and then in a large validation cohort. Rare PNPLA3 variants were not detected by sequencing coding regions and intron-exon boundaries either in 142 patients with early-onset NAFLD nor in 100 healthy individuals with alanine aminotransferase22/20 IU/mL. …

AdultMale0301 basic medicinemedicine.medical_specialtyAdolescentPolymorphism Single Nucleotide03 medical and health sciences0302 clinical medicineNon-alcoholic Fatty Liver DiseaseLipid dropletInternal medicineNonalcoholic fatty liver diseasemedicineHumansGenetic Predisposition to DiseaseAlleleChildGeneticsHepatologybiologyMembrane ProteinsAlanine TransaminaseLipaseMiddle AgedHepatologyLipid Metabolismmedicine.diseasedigestive system diseases030104 developmental biologyEndocrinologyHaplotypesLiverAlanine transaminasePatatin-like phospholipaseadolescent; adult; alanine transaminase; case-control studies; child; female; genetic predisposition to disease; haplotypes; humans; lipase; lipid metabolism; liver; male; membrane proteins; middle aged; non-alcoholic fatty liver disease; polymorphism; single nucleotide; hepatologyCase-Control Studiesbiology.proteinFemale030211 gastroenterology & hepatologySteatosisSteatohepatitis
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