title: Cannabinoid receptor type 2 functional variant influences liver damage in children with non-alcoholic fatty liver disease.
abstract: Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum of disease ranging from simple steatosis to inflammatory steatohepatitis (NASH) with different degrees of fibrosis that can ultimately progress to cirrhosis. Accumulating evidence suggests the involvement of the endocannabinoid-system in liver disease and related complications. In particular, hepatoprotective properties for Cannabinoid Receptor type 2 (CB2) have been shown both through experimental murine models of liver injury and association study between a CB2 functional variant, Q63R, and liver enzymes in Italian obese children with steatosis.Here, in order to clarify the role of CB2 in severity of childhood NAFLD, we have investigated the association of the CB2 Q63R variant, with histological parameters of liver disease severity in 118 Italian children with histologically-proven NAFLD.CB2 Q63R genotype was assigned performing a TaqMan assay and a general linear model analysis was used to evaluate the association between the polymorphism and the histological parameters of liver damage.We have found that whereas CB2 Q63R variant is not associated with steatosis or fibrosis, it is associated with the severity of the inflammation (p = 0.002) and the presence of NASH (p = 0.02).Our findings suggest a critical role for CB2 Q63R variant in modulating hepatic inflammation state in obese children and in the consequent increased predisposition of these patients to liver damage.
authors.affiliation: Department of Pediatrics, Second University of Naples, Naples, Italy. fra.rossi76@libero.it
authors.forename: Francesca
authors.initials: F
authors.lastname: Rossi
authors.forename: Giulia
authors.initials: G
authors.lastname: Bellini
authors.forename: Anna
authors.initials: A
authors.lastname: Alisi
authors.forename: Arianna
authors.initials: A
authors.lastname: Alterio
authors.forename: Sabatino
authors.initials: S
authors.lastname: Maione
authors.forename: Laura
authors.initials: L
authors.lastname: Perrone
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Emanuele
authors.initials: E
authors.lastname: Miraglia del Giudice
authors.forename: Valerio
authors.initials: V
authors.lastname: Nobili
mesh_terms: D000293:Adolescent; D002648:Child; D005234:Fatty Liver / Q000235:genetics* / Q000473:pathology*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics*
chemical_list: D043885:Receptor, Cannabinoid, CB2