Search results for "polymorph"

showing 10 items of 2115 documents

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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Dual therapy with peg-interferon and ribavirin in thalassemia major patients with chronic HCV infection: Is there still an indication?

2016

Background: Iron overload and hepatitis C virus (HCV) infection together can lead to chronic liver damage in thalassemia major (TM) patients. Aims: We investigated viral, genetic, and disease factors influencing sustained virological response (SVR) after peg-interferon and ribavirin therapy in TM patients with HCV infection. Methods: We analyzed 230 TM patients with HCV infection (mean age 36.0 ± 6.3 years; 59.1% genotype 1; 32.2% genotype 2; 3.4% genotype 3; and 5.3% genotype 4; 28.7% carried CC allele of rs12979860 in IL28B locus; 79.6% had chronic hepatitis and 20.4% cirrhosis; 63.5% naive and 36.5% previously treated with interferon alone) treated in 14 Italian centers. Results: By mul…

Liver Cirrhosis0301 basic medicineMaleCirrhosisThalassemiaHepacivirusCirrhosis; Hepatitis C virus; IL28B polymorphisms; Iron liver overload; Peg-interferon; Ribavirin; Sustained virological response; Thalassemia major; Adult; Antiviral Agents; Drug Therapy Combination; Female; Heart Diseases; Hepacivirus; Hepatitis C Chronic; Humans; Interferon-alpha; Interleukins; Italy; Liver Cirrhosis; Logistic Models; Male; Multivariate Analysis; Polymorphism Single Nucleotide; Retrospective Studies; Ribavirin; Treatment Outcome; Viral Load; beta-Thalassemiamedicine.disease_causeGastroenterologychemistry.chemical_compound0302 clinical medicineRetrospective StudieThalassemia majorMultivariate AnalysiGastroenterologyBeta thalassemiaHepatitis CViral LoadSustained virological responseHeart DiseaseTreatment OutcomeItaly030211 gastroenterology & hepatologyDrug Therapy CombinationFemaleViral loadHumanAdultmedicine.medical_specialtyHeart DiseasesLogistic ModelHepatitis C virusLiver CirrhosiAlpha interferonIL28B polymorphismAntiviral AgentsPolymorphism Single Nucleotide03 medical and health sciencesIron liver overloadInternal medicineRibavirinmedicineHumansRetrospective StudiesAntiviral AgentCirrhosiHepaciviruPeg-interferonHepatologybusiness.industryInterleukinsRibavirinbeta-ThalassemiaInterferon-alphaHepatitis C ChronicInterleukinmedicine.diseaseLogistic Models030104 developmental biologychemistryMultivariate AnalysisImmunologyInterferonsbusinessHepatitis C viru
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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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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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MERTK rs4374383 polymorphism affects the severity of fibrosis in non-alcoholic fatty liver disease

2015

Background & Aim Homozygosity for a common non-coding rs4374383 G>A polymorphism in MERTK (myeloid-epithelial-reproductive tyrosine kinase) has been associated with the protection against fibrosis progression in chronic hepatitis C. The main study objective was to assess whether MERTK AA genotype influences liver fibrosis, and secondarily MERTK expression in patients with non-alcoholic fatty liver disease (NAFLD). We also investigated whether MERTK is expressed in human hepatic stellate cells (HSC) and in murine models of fibrogenesis. Methods We considered 533 consecutive patients who underwent liver biopsy for suspected non-alcoholic steatohepatitis (NASH) without severe obesity from two …

Liver CirrhosisMale0301 basic medicineMessengerMice0302 clinical medicineNon-alcoholic Fatty Liver DiseaseFibrosisInbred BALB CCells CulturedMice Inbred BALB CCulturedmedicine.diagnostic_testMedicine (all)Fatty liverNASHMiddle AgedLiver biopsyFemale030211 gastroenterology & hepatologyAdultmedicine.medical_specialtyMERTKCellsBiology03 medical and health sciencesGeneticProto-Oncogene ProteinsInternal medicinemedicineAnimalsHumansFibrosis; MERTK; NASH; Adult; Animals; Cells Cultured; Female; Humans; Liver Cirrhosis; Male; Mice Inbred BALB C; Middle Aged; Non-alcoholic Fatty Liver Disease; Proto-Oncogene Proteins; RNA Messenger; Receptor Protein-Tyrosine Kinases; Polymorphism Genetic; Medicine (all); HepatologyRNA MessengerPolymorphismPolymorphism Geneticc-Mer Tyrosine KinaseHepatologyGAS6Receptor Protein-Tyrosine Kinasesnafld fibrosis mertkMERTKHepatologymedicine.diseaseFibrosis030104 developmental biologyImmunologyHepatic stellate cellRNASteatohepatitisJournal of Hepatology
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IL-6 -174G/C polymorphism and IL-6 serum levels in patients with liver cirrhosis and hepatocellular carcinoma.

2011

Recently, a link between high levels of circulating IL-6 and hepatocellular carcinoma (HCC) has been proposed. In addition, single nucleotide polymorphisms (SNPs) in the promoter region of the IL-6 gene have been reported to be related to several inflammatory-related conditions, including cancer. The purpose of this article is: (1) to evaluate the frequencies of SNPs in the IL-6 promoter region at position -174 and IL-6 serum levels in a group of patients with HCC and underlying liver cirrhosis (LC), and compare them with a group of LC patients without HCC; (2) to determine whether a possible correlation exists between the allelic variations, IL-6 serum levels, and the risk of developing HC…

Liver CirrhosisMaleCirrhosisCarcinoma HepatocellularGenotypeSNPSingle-nucleotide polymorphismEnzyme-Linked Immunosorbent AssayBioinformaticsBiochemistryPolymerase Chain ReactionPolymorphism Single NucleotideGene FrequencyGeneticsmedicineHumansAlleleHCCInterleukin 6Molecular BiologyGeneIL-6biologyInterleukin-6Liver NeoplasmsPromotermedicine.diseaseHepatocellular carcinomabiology.proteinCancer researchIL-6 -174G/C polymorphism liver cirrhosis hepatocellular carcinomaMolecular MedicineFemaleRestriction fragment length polymorphismPolymorphism Restriction Fragment LengthBiotechnology
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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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PNPLA3 rs738409 I748M is associated with steatohepatitis in 434 non-obese subjects with hepatitis C

2015

Summary Background The PNPLA3/Adiponutrin rs738409 C/G single nucleotide polymorphism is associated with the severity of steatosis, steatohepatitis and fibrosis in patients with non-alcoholic fatty liver disease, as well as the severity of steatosis and fibrosis in patients with chronic hepatitis C (CHC). Aim To test in genotype 1(G1)-CHC patients, the putative association between the PNPLA3 variant and histological features of steatohepatitis, as well as their impact on the severity of fibrosis. Methods Four hundred and thirty-four consecutively biopsied Caucasian G1-CHC patients were genotyped for PNPLA3 rs738409, its effect evaluated by using an additive model. Histological features of s…

Liver CirrhosisMaleHepacivirusGastroenterologyCohort StudiesNon-alcoholic Fatty Liver DiseaseFibrosisGenotypePharmacology (medical)ChronicMembrane ProteinSettore MED/12 - Gastroenterologiaeducation.field_of_studyMedicine (all)Fatty liverGastroenterologySingle NucleotideHepatitis CMiddle AgedHepatitis CFemaleHumanAdultmedicine.medical_specialtyLogistic ModelGenotypeLiver CirrhosiEuropean Continental Ancestry GroupSingle-nucleotide polymorphismSettore MED/08 - Anatomia PatologicaPolymorphism Single NucleotideWhite PeopleInternal medicinemedicineHumansAdiponutrinObesityPolymorphismeducationAdult; Cohort Studies; European Continental Ancestry Group; Fatty Liver; Female; Genotype; Hepacivirus; Hepatitis C Chronic; Humans; Lipase; Liver Cirrhosis; Logistic Models; Male; Membrane Proteins; Middle Aged; Non-alcoholic Fatty Liver Disease; Obesity; Polymorphism Single Nucleotide; Pharmacology (medical); Medicine (all)HepaciviruHepatologybusiness.industryMembrane ProteinsLipaseHepatitis C Chronicmedicine.diseaseFatty LiverLogistic ModelsCohort StudieSteatosisSteatohepatitisbusinessAlimentary Pharmacology &amp; Therapeutics
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Role of IL-28B and inosine triphosphatase polymorphisms in efficacy and safety of Peg-Interferon and ribavirin in chronic hepatitis C compensated cir…

2013

Genetic factors can influence the outcome of antiviral therapy in chronic hepatitis C (HCV). We evaluated the role of interleukin-28B single nucleotide polymorphisms (SNPs) and inosine triphosphatase (ITPA) gene variants in HCV cirrhosis treated with Peg-Interferon and ribavirin. A prospective cohort of 233 patients with compensated cirrhosis received 1-1.5 μg/kg/week of Peg-Interferon alpha-2b plus 1000-1200 mg/day of RBV for 48 weeks. A sustained virologic response (SVR) was achieved in 27% of patients. On multivariate logistic analysis, the absence of oesophageal varices (OR 3.64 CI 95% 1.27-10.44 P = 0.016), infection with genotype 2 or 3 (OR 4.06, CI 95% 1.08-15.26, P = 0.038), C/C all…

Liver CirrhosisMaleSettore MED/07 - Microbiologia E Microbiologia ClinicaAnemia HemolyticGenotypeHepacivirusInterferon alpha-2Esophageal and Gastric VaricesAntiviral AgentsPolymorphism Single NucleotidePolyethylene GlycolsSettore BIO/13 - Biologia ApplicataRibavirinHumanschronic hepatitis C cirrhosis IL-28B inosine triphosphatase sustained virologic responseProspective StudiesPyrophosphatasesGenetic Association StudiesAgedSettore MED/12 - GastroenterologiaDose-Response Relationship DrugInterleukinsInterferon-alphaSequence Analysis DNAHepatitis C ChronicMiddle AgedRecombinant ProteinsLogistic ModelsTreatment OutcomeMultivariate AnalysisDrug Therapy CombinationFemaleInterferonsJournal of viral hepatitis
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