Tahira Foyzun, Maddie Whiting, Kate K. Velasco, Jessie C. Jacobsen, Mark Connor, Natasha L. Grimsey
{"title":"大麻素 CB2 受体的单核苷酸多态性:分子药理学与疾病相关。","authors":"Tahira Foyzun, Maddie Whiting, Kate K. Velasco, Jessie C. Jacobsen, Mark Connor, Natasha L. Grimsey","doi":"10.1111/bph.16383","DOIUrl":null,"url":null,"abstract":"<p>Preclinical evidence implicating cannabinoid receptor 2 (CB<sub>2</sub>) in various diseases has led researchers to question whether CB<sub>2</sub> 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 <i>CNR2</i> coding exon, ~36 SNPs have high overall population prevalence (minor allele frequencies [MAF] ~37%), including non-synonymous SNP (ns-SNP) rs2501432 encoding CB<sub>2</sub> 63Q/R. Interspersed are ~27 lower frequency SNPs, four being ns-SNPs. <i>CNR2</i> introns also harbour numerous SNPs. This review summarises CB<sub>2</sub> ns-SNP molecular pharmacology and evaluates evidence from ~70 studies investigating CB<sub>2</sub> genetic variants with proposed linkage to disease. Although <i>CNR2</i> 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 <i>CNR2</i> disease links and clarify specific mechanisms linking <i>CNR2</i> genetic variation to disease pathophysiology and potential drug responses.</p>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":null,"pages":null},"PeriodicalIF":6.8000,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bph.16383","citationCount":"0","resultStr":"{\"title\":\"Single nucleotide polymorphisms in the cannabinoid CB2 receptor: Molecular pharmacology and disease associations\",\"authors\":\"Tahira Foyzun, Maddie Whiting, Kate K. Velasco, Jessie C. Jacobsen, Mark Connor, Natasha L. Grimsey\",\"doi\":\"10.1111/bph.16383\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Preclinical evidence implicating cannabinoid receptor 2 (CB<sub>2</sub>) in various diseases has led researchers to question whether CB<sub>2</sub> 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 <i>CNR2</i> coding exon, ~36 SNPs have high overall population prevalence (minor allele frequencies [MAF] ~37%), including non-synonymous SNP (ns-SNP) rs2501432 encoding CB<sub>2</sub> 63Q/R. Interspersed are ~27 lower frequency SNPs, four being ns-SNPs. <i>CNR2</i> introns also harbour numerous SNPs. This review summarises CB<sub>2</sub> ns-SNP molecular pharmacology and evaluates evidence from ~70 studies investigating CB<sub>2</sub> genetic variants with proposed linkage to disease. Although <i>CNR2</i> 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 <i>CNR2</i> disease links and clarify specific mechanisms linking <i>CNR2</i> genetic variation to disease pathophysiology and potential drug responses.</p>\",\"PeriodicalId\":9262,\"journal\":{\"name\":\"British Journal of Pharmacology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.8000,\"publicationDate\":\"2024-05-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bph.16383\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"British Journal of Pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/bph.16383\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"British Journal of Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/bph.16383","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
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.
期刊介绍:
The British Journal of Pharmacology (BJP) is a biomedical science journal offering comprehensive international coverage of experimental and translational pharmacology. It publishes original research, authoritative reviews, mini reviews, systematic reviews, meta-analyses, databases, letters to the Editor, and commentaries.
Review articles, databases, systematic reviews, and meta-analyses are typically commissioned, but unsolicited contributions are also considered, either as standalone papers or part of themed issues.
In addition to basic science research, BJP features translational pharmacology research, including proof-of-concept and early mechanistic studies in humans. While it generally does not publish first-in-man phase I studies or phase IIb, III, or IV studies, exceptions may be made under certain circumstances, particularly if results are combined with preclinical studies.