title: Association between a polymorphism in cannabinoid receptor 2 and severe necroinflammation in patients with chronic hepatitis C.
abstract: OBJECTIVE
  The cannabinoid receptor 2 (CB2) has been implicated in liver disease. The single-nucleotide polymorphism rs35761398 in cannabinoid receptor 2 gene (CNR2), which encodes the CB2, substitutes glutamine (Q) 63 with arginine (R), and reduces the function of the gene product. We investigated the effects of CNR2 rs35761398 in patients with hepatitis C virus (HCV) infection.
  
  
  METHODS
  We studied 169 consecutive patients with asymptomatic chronic hepatitis (tested positive for anti-HCV and HCV RNA) at 2 liver units in southern Italy. First, liver biopsy samples were collected from July 2009 through December 2011. All patients were naive to antiviral therapy; CNR2 genotype was determined by polymerase chain reaction analysis.
  
  
  RESULTS
  Patients with the CB2-63 QQ variant had higher serum levels of aminotransferase than those with the CB2-63 QR or RR variants; they also had higher histologic activity index (HAI) scores (8.6 ± 3.8) than patients without the CB2-63 RR variant (5.3 ± 3.6; P < .005) or those with the CB2-63 QR variant (5.8 ± 3.3; P < .001). Patients with the different variants of CNR2 did not differ in fibrosis stage or steatosis score. Moderate or severe chronic hepatitis (HAI score, >8) was identified more frequently (55.5%) in patients with the CB2-63 QQ variant than in those with the 63 QR (20%; P < .005) or RR variants (17.4%; P < .005). In logistic regression analysis, the CB2-63 QQ variant and fibrosis score were independent predictors of moderate or severe chronic hepatitis (HAI score, >8; P < .0001).
  
  
  CONCLUSIONS
  The CB2-63 QQ variant of CNR2 is associated with more severe inflammation and hepatocellular necrosis in patients with HCV infection.
authors.affiliation: Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy. Electronic address: nicola.coppola@unina2.it.
authors.forename: Nicola
authors.initials: N
authors.lastname: Coppola
authors.affiliation: Internal Medicine and Hepatology, Second University of Naples, Naples, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Zampino
authors.affiliation: Department of Experimental Medicine, Second University of Naples, Naples, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Bellini
authors.affiliation: Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Macera
authors.affiliation: Internal Medicine and Hepatology, Second University of Naples, Naples, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Marrone
authors.affiliation: Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy.
authors.forename: Mariantonietta
authors.initials: M
authors.lastname: Pisaturo
authors.affiliation: Internal Medicine and Hepatology, Second University of Naples, Naples, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Boemio
authors.affiliation: Department of Pediatrics, Second University of Naples, Naples, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Nobili
authors.affiliation: Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pasquale
authors.affiliation: Department of Experimental Medicine, Second University of Naples, Naples, Italy.
authors.forename: Sabatino
authors.initials: S
authors.lastname: Maione
authors.affiliation: Internal Medicine and Hepatology, Second University of Naples, Naples, Italy.
authors.forename: Luigi Elio
authors.initials: LE
authors.lastname: Adinolfi
authors.affiliation: Department of Pediatrics, Second University of Naples, Naples, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Perrone
authors.affiliation: Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy.
authors.forename: Evangelista
authors.initials: E
authors.lastname: Sagnelli
authors.affiliation: Department of Pediatrics, Second University of Naples, Naples, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Miraglia Del Giudice
authors.affiliation: Department of Pediatrics, Second University of Naples, Naples, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Rossi
mesh_terms: D058070:Asymptomatic Diseases; D018450:Disease Progression; D005260:Female; D019698:Hepatitis C, Chronic / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000473:pathology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics*; D019562:Viral Load
chemical_list: C588309:CNR2 protein, human; D043885:Receptor, Cannabinoid, CB2
keywords: ALT; AST; CB; CHC; CNR; Cannabinoid System; Disease Progression; Genetics; HAI; HCV; HDV; HSC; Histologic Activity Index; PCR; Q; R; SNP; alanine aminotransferase; arginine; aspartate aminotransferase; cannabinoid receptor; cannabinoid receptor 2; chronic hepatitis C; glutamine; hepatic stellate cell; hepatitis C virus; hepatitis delta virus; polymerase chain reaction