Genetic association between bipolar disorder and 524A>C (Leu133Ile) polymorphism of CNR2 gene, encoding for CB2 cannabinoid receptor

J Affect Disord. 2011 Nov;134(1-3):427-30. doi: 10.1016/j.jad.2011.05.023. Epub 2011 Jun 11.


Introduction: 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.

Conclusion: Though further investigations are necessary to confirm this data, our results suggest that CB2 cannabinoid receptor may play a role in BD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Amidohydrolases / genetics
  • Amidohydrolases / metabolism
  • Bipolar Disorder / genetics*
  • Cannabinoid Receptor Modulators / genetics
  • Case-Control Studies
  • Depressive Disorder, Major / genetics
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Male
  • Mutation, Missense
  • Polymorphism, Genetic
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide
  • Receptor, Cannabinoid, CB1 / genetics
  • Receptor, Cannabinoid, CB1 / metabolism
  • Receptor, Cannabinoid, CB2 / genetics*
  • Receptor, Cannabinoid, CB2 / metabolism
  • Schizophrenia / genetics


  • Cannabinoid Receptor Modulators
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • Amidohydrolases
  • fatty-acid amide hydrolase