Single nucleotide polymorphisms in the cannabinoid CB2 receptor: Molecular pharmacology and disease associations

Preclinical evidence implicating cannabinoid receptor 2 (CB2) in various diseases has led researchers to question whether CB2 genetics influence aetiology or progression. Associations between conditions and genetic loci are often studied via single nucleotide polymorphism (SNP) prevalence in case versus control populations. In the CNR2 coding exon, 36 SNPs have high overall population prevalence (minor allele frequencies [MAF] 37%), including non-synonymous SNP (ns-SNP) rs2501432 encoding CB2 63Q/R. Interspersed are 27 lower frequency SNPs, four being ns-SNPs. CNR2 introns also harbour numerous SNPs. This review summarises CB2 ns-SNP molecular pharmacology and evaluates evidence from 70 studies investigating CB2 genetic variants with proposed linkage to disease. Although CNR2 genetic variation has been associated with a wide variety of conditions, including osteoporosis, immune-related disorders, and mental illnesses, further work is required to robustly validate CNR2 disease links and clarify specific mechanisms linking CNR2 genetic variation to disease pathophysiology and potential drug responses.