Search results for "Disposition"

showing 10 items of 832 documents

Genome wide identification of new genes and pathways in patients with both autoimmune thyroiditis and type 1 diabetes

2015

Autoimmune thyroid diseases (AITD) and Type 1 diabetes (T1D) frequently occur in the same individual pointing to a strong shared genetic susceptibility. Indeed, the co-occurrence of T1D and AITD in the same individual is classified as a variant of the autoimmune polyglandular syndrome type 3 (designated APS3v). Our aim was to identify new genes and mechanisms causing the co-occurrence of T1D + AITD (APS3v) in the same individual using a genome-wide approach. For our discovery set we analyzed 346 Caucasian APS3v patients and 727 gender and ethnicity matched healthy controls. Genotyping was performed using the Illumina Human660W-Quad.v1. The replication set included 185 APS3v patients and 340…

Linkage disequilibriumT-LymphocytesImmunologyLocus (genetics)Genome-wide association studyHuman leukocyte antigenBiologyArticleLinkage DisequilibriumAutoimmune thyroiditisGenetic predispositionmedicineHumansImmunology and AllergyCTLA-4 AntigenGenetic Predisposition to DiseaseCD40 AntigensPolyendocrinopathies AutoimmuneGenotypingGenetic associationGeneticsB-LymphocytesHistocompatibility Antigens Class IHistocompatibility Antigens Class IIThyroiditis AutoimmuneProtein Tyrosine Phosphatase Non-Receptor Type 22medicine.diseaseDiabetes Mellitus Type 1ImmunologyGenome-Wide Association StudyJournal of Autoimmunity
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Association Between PNPLA3 rs738409 C>G Variant and Liver-Related Outcomes in Patients with Non-alcoholic Fatty Liver Disease

2020

Background & Aims Patients with nonalcoholic fatty liver disease (NAFLD) have an increased risk for liver-related complications, such as decompensation, hepatocellular carcinoma (HCC), and death; the severity of liver fibrosis and metabolic comorbidities are the main risk factors. A single nucleotide polymorphism in patatin-like phospholipase domain-containing-3 (PNPLA3) gene is associated with higher prevalence of liver damage and HCC, but there are no data from prospective studies of outcomes of patients with this polymorphism. We investigated whether the common rs738409 variant in PNPLA3 gene associates with the occurrence of liver-related events and death in a large cohort of patients w…

Liver Cancermedicine.medical_specialtyCirrhosisCarcinoma HepatocellularGenotypeGastroenterologyPolymorphism Single Nucleotide03 medical and health sciences0302 clinical medicineNon-alcoholic Fatty Liver DiseaseInternal medicineNonalcoholic fatty liver diseasemedicineHumansDecompensationGenetic Predisposition to DiseaseProspective StudiesProspective cohort studyHepatologyProportional hazards modelbusiness.industryPrognostic FactorRisk FactorHazard ratioLiver NeoplasmsGastroenterologyMembrane ProteinsLong-Term OutcomeLipasemedicine.disease030220 oncology & carcinogenesisHepatocellular carcinoma030211 gastroenterology & hepatologybusinessLiver cancer
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International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways

2015

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10−8) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine–cytokine pathways, for which relevant therapies exist.

Liver CirrhosisGenetics and Molecular Biology (all)pathogenesirisk assessment EMTREE medical terms: Articlegenetic associationgenotypeEMTREE drug terms: chemokine receptor CCR6genetic riskBiochemistrymeta-analysiprimary biliary cirrhosichemokine receptor CCR6 [EMTREE drug terms]single nucleotide polymorphismgenetic variabilityArticle [risk assessment EMTREE medical terms]Liver Cirrhosis BiliarypathogenesisBiliaryChemistry (all)STAT protein GEOBASE Subject Index: disease treatmentcohort analysisgenome wide meta analysis PBCsignal transductiongene locuscohort analysiCBPArticle*Physics and Astronomy (all)macrophage inflammatory protein 3alphaHumanscontrolled studyhumaninterleukin 27genomeBiochemistry Genetics and Molecular Biology (all)meta analysiinterleukin 12p40EMTREE drug terms: chemokine receptor CCR6; interleukin 12; interleukin 12p40; interleukin 27; Janus kinase; macrophage inflammatory protein 3alpha; STAT protein GEOBASE Subject Index: disease treatment; genome; meta-analysis; pathogen; risk assessment EMTREE medical terms: Article; cohort analysis; controlled study; gene locus; genetic association; genetic predisposition; genetic risk; genetic variability; genotype; human; major clinical study; meta analysis; pathogenesis; primary biliary cirrhosis; signal transduction; single nucleotide polymorphismmajor clinical studyprimary biliary cirrhosismeta-analysisdisease treatment [STAT protein GEOBASE Subject Index]Biochemistry Genetics and Molecular Biology (all); Chemistry (all); Physics and Astronomy (all)Humans; Liver Cirrhosis; Biliary; Genome-Wide Association Study; Biochemistry; Genetics and Molecular Biology (all); Chemistry (all); Physics and Astronomy (all)gene locuinterleukin 12genetic predispositionJanus kinasepathogenmeta analysisHumans; Liver Cirrhosis Biliary; Genome-Wide Association Study; Biochemistry Genetics and Molecular Biology (all); Chemistry (all); Physics and Astronomy (all)Genome-Wide Association Study
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Liver Fibrosis and Metabolic Alterations in Adults With alpha-1-antitrypsin Deficiency Caused by the Pi*ZZ Mutation

2019

Background & Aims Alpha-1 antitrypsin deficiency (AATD) is among the most common genetic disorders. Severe AATD is caused by a homozygous mutation in the SERPINA1 gene that encodes the Glu342Lys substitution (called the Pi*Z mutation, Pi*ZZ genotype). Pi*ZZ carriers may develop lung and liver diseases. Mutation-associated lung disorders have been well studied, but less is known about the effects in liver. We assessed the liver disease burden and associated features in adults with this form of AATD. Methods We collected data from 554 Pi*ZZ adults (403 in an exploratory cohort, 151 in a confirmatory cohort), in 9 European countries, with AATD who were homozygous for the Pi*Z mutation, and 234…

Liver CirrhosisMale0301 basic medicineALTLiver diseasechemistry.chemical_compound0302 clinical medicineLiver Function TestsRisk FactorsGenotypeRare Liver DiseaseAlpha 1-antitrypsin deficiencyHomozygoteAge FactorsGastroenterologyMiddle AgedEuropeEditorial CommentaryPhenotypemedicine.anatomical_structureLiverElasticity Imaging TechniquesFemale030211 gastroenterology & hepatologyTEAdultmedicine.medical_specialty610Mice Transgenic03 medical and health sciencesSex Factorsalpha 1-Antitrypsin DeficiencyInternal medicinemedicinePiAnimalsHumansGenetic Predisposition to DiseaseASTAgedLungHepatologyTriglyceridebusiness.industryLipid Metabolismmedicine.diseaseFatty Liver030104 developmental biologyEndocrinologychemistryCase-Control Studiesalpha 1-AntitrypsinMutationSteatosisTransient elastographybusinessGastroenterology
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The MBOAT7-TMC4 Variant rs641738 Increases Risk of Nonalcoholic Fatty Liver Disease in Individuals of European Descent

2016

Background &amp; 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&gt;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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Fibronectin Type III Domain–Containing Protein 5 rs3480 A&gt;G Polymorphism, Irisin, and Liver Fibrosis in Patients With Nonalcoholic Fatty Liver Dis…

2017

Context Contrasting data have been reported on the role of irisin, a novel myokine encoded by the fibronectin type III domain-containing protein 5 (FNDC5) gene, in nonalcoholic fatty liver disease (NAFLD) pathogenesis. We tested in patients with suspected nonalcoholic steatohepatitis (NASH) the association of FNDC5 variants, hepatic expression, and circulating irisin with liver damage (F2 to F4 fibrosis as main outcome). We also investigated whether irisin modulates hepatocellular fat accumulation and stellate cell activation in experimental models. Methods We considered 593 consecutive patients who underwent liver biopsy for suspected NASH and 192 patients with normal liver enzymes and wit…

Liver CirrhosisMale0301 basic medicineEndocrinology Diabetes and MetabolismClinical BiochemistrySeverity of Illness IndexBiochemistryGastroenterologyMiceEndocrinologyNon-alcoholic Fatty Liver DiseaseFibrosisNonalcoholic fatty liver diseaseOdds RatioProspective StudiesCarbon Tetrachloridemedicine.diagnostic_testReverse Transcriptase Polymerase Chain ReactionHep G2 CellsMiddle AgedFNDC5LiverLiver biopsyFemaleAdultmedicine.medical_specialtyIn Vitro TechniquesDiet High-FatReal-Time Polymerase Chain ReactionPolymorphism Single Nucleotide03 medical and health sciencesDiabetes mellitusInternal medicineMyokineHepatic Stellate CellsmedicineAnimalsHumansFNDC5 IRISIN NAFLDGenetic Predisposition to Diseasebusiness.industryBiochemistry (medical)medicine.diseasedigestive system diseasesFibronectins030104 developmental biologyEndocrinologyCase-Control StudiesHepatic stellate cellSteatosisbusinessThe Journal of Clinical Endocrinology &amp; Metabolism
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Genetic susceptibility of increased intestinal permeability is associated with progressive liver disease and diabetes in patients with non-alcoholic …

2020

Abstract Background and aim Increased intestinal permeability plays a key role in the pathogenesis of fat deposition in the liver. The aim of our study was to assess whether a single nucleotide polymorphism of protein tyrosine phosphatase non-receptor type 2 (PTPN2) (rs2542151 T→G), involved in intestinal permeability, may be associated with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). Methods and results We recruited a prospective cohort of NAFLD subjects and matched controls. Clinical data, PTPN2 genotype and laboratory data were collected for each patient. Results were stratified according to liver histology and diabetes. We enrolled 566 cases and 377 co…

Liver CirrhosisMaleEndocrinology Diabetes and MetabolismMedicine (miscellaneous)030204 cardiovascular system & hematologySeverity of Illness IndexGastroenterologyLiver disease0302 clinical medicineNon-alcoholic Fatty Liver DiseaseRisk FactorsNonalcoholic fatty liver diseasePrevalenceProspective StudiesProtein Tyrosine Phosphatase Non-Receptor Type 2Nutrition and Dieteticsmedicine.diagnostic_testFatty liverMiddle AgedPhenotypeItalyLiver biopsyFemaleCardiology and Cardiovascular MedicineAdultmedicine.medical_specialtySettore MED/12 - GASTROENTEROLOGIA030209 endocrinology & metabolismIntestinal permeabilityPolymorphism Single NucleotideRisk AssessmentPermeability03 medical and health sciencesInternal medicineDiabetes mellitusmedicineGenetic susceptibilityHumansNonalcoholic fatty liver diseaseGenetic Predisposition to DiseaseGenetic Association Studiesbusiness.industryType 2 Diabetes Mellitusmedicine.diseaseCross-Sectional StudiesDiabetes Mellitus Type 2Intestinal AbsorptionCase-Control StudiesSteatosisSteatohepatitisbusiness
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Glucokinase Regulatory Protein Gene Polymorphism Affects Liver Fibrosis in Non-Alcoholic Fatty Liver Disease

2014

BACKGROUND AND AIMS: Variant in glucokinase regulatory protein (GCKR), associated with lipid and glucose traits, has been suggested to affect fatty liver infiltration. We aimed to assess whether GCKR rs780094 C-->T SNP influences the expression of steatosis, lobular inflammation and fibrosis in NAFLD patients, after correction for PNPLA3 genotype. METHODS: In 366 consecutive NAFLD patients (197 from Sicily, and 169 from center/northern Italy), we assessed anthropometric, biochemical and metabolic features; liver biopsy was scored according to Kleiner. PNPLA3 rs738409 C>G and GCKR rs780094 C>T single nucleotide polymorphisms were also assessed. RESULTS: At multivariate logistic regression an…

Liver CirrhosisMalelcsh:MedicineNonalcoholic SteatohepatitisGene FrequencyFibrosisMedicineProspective Studieslcsh:ScienceSicilyliver fibrosisSettore MED/12 - GastroenterologiaMultidisciplinarymedicine.diagnostic_testGlucokinase regulatory proteinbiologyLiver DiseasesFatty liverMiddle Aged3. Good healthItalyLiver biopsyMedicineFemaleResearch ArticleAdultmedicine.medical_specialtyNAFLD GCKRGenotypeGENETICSgene polymorphismSingle-nucleotide polymorphismGastroenterology and HepatologyGLUCKINASESettore MED/08 - Anatomia PatologicaPolymorphism Single NucleotideNAFLDInternal medicineHumansGenetic Predisposition to DiseaseBiologySettore MED/42 - IGIENE GENERALE E APPLICATATriglyceridesPNPLA3Adaptor Proteins Signal TransducingEvolutionary BiologyPopulation Biologybusiness.industrylcsh:RSettore MED/09 - MEDICINA INTERNAComputational BiologyMembrane Proteinsnon-alcoholic fatty liver diseaseLipasePolymorphysmmedicine.diseaseLogistic ModelsEndocrinologyMetabolic DisordersMultivariate AnalysisGenetic Polymorphismbiology.proteinlcsh:QGlucokinase regulatory proteinGene polymorphismSteatosisSteatohepatitisbusinessPopulation GeneticsSteatohepatiti
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Thrombophilic genetic factors PAI-1 4G-4G and MTHFR 677TT as risk factors of alcohol, cryptogenic liver cirrhosis and portal vein thrombosis, in a Ca…

2015

The thrombophilic genetic factors (THRGFs), PAI-1 4G-4G, MTHFR 677TT, V Leiden 506Q and Prothrombin 20210A, were studied as risk factors in 865 Caucasian patients with liver cirrhosis, consecutively enrolled from June 2008 to January 2014. A total of 582 HCV, 80 HBV, 94 alcohol, (82 with more than one etiologic factor) and 191 cryptogenic patients with liver cirrhosis had been consecutively enrolled; 243 patients showed portal vein thrombosis (PVT). At least one of the above THRGFs was present in 339/865 patients (39.2%). PAI-1 4G-4G and MTHFR 677TT were the most frequent THRGFs, statistically significant in patients with alcohol, cryptogenic liver cirrhosis, and PVT: respectively 24 and 28…

Liver CirrhosisMalemedicine.medical_specialtyAlcoholic liver diseaseCirrhosisAlcohol DrinkingAlcoholThrombophiliaLogistic regressionGastroenterologyPolymorphism Single NucleotideWhite Peoplechemistry.chemical_compoundRisk FactorsInternal medicineGenotypePlasminogen Activator Inhibitor 1GeneticsmedicineHumansGenetic Predisposition to DiseaseGenetic Association StudiesMethylenetetrahydrofolate Reductase (NADPH2)Venous ThrombosisbiologyPortal VeinGeneral Medicinemedicine.diseasedigestive system diseasesPortal vein thrombosischemistryMethylenetetrahydrofolate reductasebiology.proteinFemaleGene
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Genetic association of interleukin-6 polymorphism (-174 G/C) with chronic liver diseases and hepatocellular carcinoma

2012

Interleukin-6 (IL-6) is a pleiotropic cytokine which is expressed in many inflammatory cells in response to different types of stimuli, regulating a number of biological processes. The IL-6 gene is polymorphic in both the 5’ and 3’ flanking regions and more than 150 single nucleotide polymorphisms have been identified so far. Genetic polymorphisms of IL-6 may affect the outcomes of several diseases, where the presence of high levels of circulating IL-6 have been correlated to the stage and/or the progression of the disease itself. The -174 G/C polymorphism is a frequent polymorphism, that is located in the upstream regulatory region of the IL-6 gene and affects IL-6 production. However, the…

Liver Cirrhosismedicine.medical_specialtyCarcinoma HepatocellularHepatitis C virusSingle-nucleotide polymorphismBiologyChronic liver diseasemedicine.disease_causePolymorphism Single NucleotideGastroenterologyHepatitis B ChronicNon-alcoholic Fatty Liver DiseaseRisk FactorsChronic hepatitis Hepatocellular carcinoma Interleukin-6 Liver cirrhosis Single nucleotide polymorphismsInternal medicineGenotypemedicineHumansGenetic Predisposition to DiseaseTopic HighlightLiver Diseases AlcoholicInterleukin-6Liver NeoplasmsFatty liverGastroenterologyGeneral MedicineHepatitis C ChronicHepatitis Bmedicine.diseaseFatty LiverHepatitis AutoimmunePhenotypeHepatocellular carcinomaImmunologySteatohepatitisWorld Journal of Gastroenterology
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