Cannabinoid Receptor Type 2 Functional Variant Influences Liver Damage in Children with Non-Alcoholic Fatty Liver Disease 英文参考文献.docVIP

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Cannabinoid Receptor Type 2 Functional Variant Influences Liver Damage in Children with Non-Alcoholic Fatty Liver Disease 英文参考文献.doc

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Cannabinoid Receptor Type 2 Functional Variant Influences Liver Damage in Children with Non-Alcoholic Fatty Liver Disease 英文参考文献

CannabinoidReceptorType2FunctionalVariant InfluencesLiverDamageinChildrenwithNon-Alcoholic FattyLiverDisease FrancescaRossi1,3*,GiuliaBellini2,AnnaAlisi4,AriannaAlterio4,SabatinoMaione2,LauraPerrone1, FrancoLocatelli3,5,EmanueleMiragliadelGiudice1.,ValerioNobili4. 1DepartmentofPediatrics,SecondUniversityofNaples,Naples,Italy,2DepartmentofExperimentalMedicine,SecondUniversityofNaples,Naples,Italy,3Departmentof Haematology-Oncology, Bambino Gesu` Children’s Hospital and Research Institute, Rome, Italy, 4Liver Unit, Bambino Gesu` Children’s Hospital and Research Institute, Rome,Italy,5UniversityofPavia,Pavia,Italy Abstract Non-alcoholicfattyliverdisease(NAFLD)comprisesaspectrumofdiseaserangingfromsimplesteatosistoinflammatory steatohepatitis(NASH)withdifferentdegreesoffibrosisthatcanultimatelyprogresstocirrhosis.Accumulatingevidence suggests the involvement of the endocannabinoid-system in liver disease and related complications. In particular, hepatoprotectivepropertiesforCannabinoidReceptortype2(CB2)havebeenshownboththroughexperimentalmurine models of liver injury and association study between a CB2 functional variant, Q63R, and liver enzymes in Italian obese childrenwithsteatosis. Here,inordertoclarifytheroleofCB2inseverityofchildhoodNAFLD,wehaveinvestigatedthe association of the CB2 Q63R variant, with histological parameters of liver disease severity in 118 Italian children with histologically-provenNAFLD. CB2Q63RgenotypewasassignedperformingaTaqManassayandagenerallinearmodel analysis was used to evaluate the association between the polymorphism and the histological parameters of liver damage. WehavefoundthatwhereasCB2Q63Rvariantisnotassociatedwithsteatosisorfibrosis,itisassociatedwiththe severityoftheinflammation(p=0.002)andthepresenceofNASH(p=0.02). OurfindingssuggestacriticalroleforCB2 Q63Rvariantinmodulatinghepaticinflammationstateinobesechildrenandintheconsequentincreasedpredispositionof thesepatientstoliverdamage. Citation:RossiF,BelliniG,AlisiA,A