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

被引:2
作者
Foyzun, Tahira [1 ]
Whiting, Maddie [2 ,3 ]
Velasco, Kate K. [2 ,3 ]
Jacobsen, Jessie C. [4 ,5 ]
Connor, Mark [1 ]
Grimsey, Natasha L. [2 ,5 ,6 ]
机构
[1] Macquarie Univ, Fac Med Hlth & Human Sci, Macquarie Med Sch, N Ryde, NSW, Australia
[2] Univ Auckland, Fac Med & Hlth Sci, Sch Med Sci, Dept Pharmacol & Clin Pharmacol, Auckland, New Zealand
[3] Univ Auckland, Sch Med, Fac Med & Hlth Sci, Dept Med, Auckland, New Zealand
[4] Univ Auckland, Fac Sci, Sch Biol Sci, Auckland, New Zealand
[5] Univ Auckland, Ctr Brain Res, Auckland, New Zealand
[6] Maurice Wilkins Ctr Mol Biodiscovery, Auckland, New Zealand
关键词
biological variation; population; biomarkers; drug development; genetics; polymorphism; single nucleotide; receptor; cannabinoid; CB2; signal transduction; BONE-MINERAL DENSITY; GENOME-WIDE ASSOCIATION; CNR2; GENE; OSTEOPOROSIS SUSCEPTIBILITY; ENDOCANNABINOID SYSTEM; LIVER-DISEASE; IMMUNE THROMBOCYTOPENIA; COMMON VARIANTS; CONCISE GUIDE; Q63R VARIANT;
D O I
10.1111/bph.16383
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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, similar to 36 SNPs have high overall population prevalence (minor allele frequencies [MAF] similar to 37%), including non-synonymous SNP (ns-SNP) rs2501432 encoding CB2 63Q/R. Interspersed are similar to 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 similar to 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.
引用
收藏
页码:2391 / 2412
页数:22
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