Single nucleotide polymorphisms in the cannabinoid CB 2 receptor: Molecular pharmacology and disease associations.

Autor: Foyzun T; Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, North Ryde, New South Wales, Australia., Whiting M; Department of Pharmacology and Clinical Pharmacology, School of Medical Sciences, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.; Department of Medicine, School of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand., Velasco KK; Department of Pharmacology and Clinical Pharmacology, School of Medical Sciences, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.; Department of Medicine, School of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand., Jacobsen JC; School of Biological Sciences, Faculty of Science, University of Auckland, Auckland, New Zealand.; Centre for Brain Research, University of Auckland, Auckland, New Zealand., Connor M; Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, North Ryde, New South Wales, Australia., Grimsey NL; Department of Pharmacology and Clinical Pharmacology, School of Medical Sciences, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.; Centre for Brain Research, University of Auckland, Auckland, New Zealand.; Maurice Wilkins Centre for Molecular Biodiscovery, Auckland, New Zealand.
Jazyk: angličtina
Zdroj: British journal of pharmacology [Br J Pharmacol] 2024 Aug; Vol. 181 (15), pp. 2391-2412. Date of Electronic Publication: 2024 May 27.
DOI: 10.1111/bph.16383
Abstrakt: Preclinical evidence implicating cannabinoid receptor 2 (CB 2 ) in various diseases has led researchers to question whether CB 2 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 CB 2 63Q/R. Interspersed are ~27 lower frequency SNPs, four being ns-SNPs. CNR2 introns also harbour numerous SNPs. This review summarises CB 2 ns-SNP molecular pharmacology and evaluates evidence from ~70 studies investigating CB 2 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.
(© 2024 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)
Databáze: MEDLINE
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