6533b861fe1ef96bd12c5992

RESEARCH PRODUCT

Glucokinase Regulatory Protein Gene Polymorphism Affects Liver Fibrosis in Non-Alcoholic Fatty Liver Disease

Antonio GriecoDi Marco VitoChiara RossoAntonio CraxìLuca MieleMaria Rosaria PipitoneSalvatore PettaDaniela CabibiElisabetta BugianesiCalogero CammàStefania GrimaudoStefania BocciaGiulio Marchesini

subject

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

description

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 analysis in the entire NAFLD cohort, the presence of significant liver fibrosis (>F1) was independently linked to high HOMA (OR 1.12, 95% CI 1.01-1.23, p = 0.02), NAFLD activity score >/= 5 (OR 4.09, 95% CI 2.45-6.81, pT SNP (OR 2.06, 95% CI 1.43-2.98, pT SNP was also associated with higher serum triglycerides (ANOVA, p = 0.02) in the entire cohort. CONCLUSIONS: In patients with NAFLD, GCKR rs780094 C>T is associated with the severity of liver fibrosis and with higher serum triglyceride levels.

yearjournalcountryeditionlanguage
2014-01-01
10.1371/journal.pone.0087523http://hdl.handle.net/2318/142647