title: Genetic association between bipolar disorder and 524A>C (Leu133Ile) polymorphism of CNR2 gene, encoding for CB2 cannabinoid receptor.
abstract: BACKGROUND
  Several studies provided evidence that the endocannabinoid system (ECS) is involved in psychiatric diseases, like major depression, schizophrenia and bipolar disorder (BD), mainly focusing on CB1 cannabinoid receptor, and FAAH, the fatty acid amide hydrolase involved in endocannabinoid metabolism. In this study we investigated the possible association of BD with three missense SNPs, of the gene CNR2, encoding for CB2 cannabinoid receptor.
  
  
  METHODS
  The possible association between BD and three CNR2 missense SNPs, namely rs2501432 (315A>G; Arg63Gln), rs41311993 (524C>A; Leu133Ile) and rs2229579 (1073C>T; Tyr316His), was investigated through a case-control study. Eighty patients and one hundred and sixty healthy subjects were recruited. Allele Specific Oligonucleotide (ASO)-PCR and restriction fragment length polymorphism (RFLP) methods were used for genotyping.
  
  
  RESULTS
  A statistically significant association was found between BD and the CNR2 524C>A; Leu133Ile (P(χ(2)) = 0.001; OR = 4.74; 95% C.I. = 2.52-10.50) while no statistically significant difference between BD and control group was observed for the other two SNPs.
  
  
  CONCLUSIONS
  Though further investigations are necessary to confirm this data, our results suggest that CB2 cannabinoid receptor may play a role in BD.
authors.affiliation: Dept of Psychiatry, Unit of Neurobiology, Pharmacology and Biotechnology, University of Pisa, Pisa, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Minocci
authors.forename: J
authors.initials: J
authors.lastname: Massei
authors.forename: A
authors.initials: A
authors.lastname: Martino
authors.forename: M
authors.initials: M
authors.lastname: Milianti
authors.forename: L
authors.initials: L
authors.lastname: Piz
authors.forename: D
authors.initials: D
authors.lastname: Di Bello
authors.forename: A
authors.initials: A
authors.lastname: Sbrana
authors.forename: E
authors.initials: E
authors.lastname: Martinotti
authors.forename: A M
authors.initials: AM
authors.lastname: Rossi
authors.forename: P
authors.initials: P
authors.lastname: Nieri
mesh_terms: D000328:Adult; D000483:Alleles; D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism; D001714:Bipolar Disorder / Q000235:genetics*; D063385:Cannabinoid Receptor Modulators / Q000235:genetics; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics* / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D063385:Cannabinoid Receptor Modulators; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D000099252:Fatty Acid Amide Hydrolases