Journal
PHARMACOGENOMICS
Volume 9, Issue 11, Pages 1647-1656Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/14622416.9.11.1647
Keywords
CNR1; genetic association; haplotype; HDL; high-density lipoprotein; LDL; low-density lipoprotein; obesity; triglyceride
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Funding
- NHLBI NIH HHS [R01 HL074168-05, R01 HL074168] Funding Source: Medline
- NIDDK NIH HHS [R01 DK080007, R01 DK080007-01A2] Funding Source: Medline
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Aims: In humans, genetic variation in endocannabinergic signaling has been associated with anthropometric measures of obesity. In randomized trials, pharmacological blockade at the level of the cannabinoid receptor 1 (CNR1) receptor not only facilitates weight reduction, but also improves insulin sensitivity and clinical measures of lipid homeostasis. We therefore tested the hypothesis that genetic variation in CNR1 is associated with common obesity-related metabolic disorders. Materials & methods: A total of six haplotype tagging SNPs were selected for CNR1, using data available within the Human HapMap (Centre d'Etude du Polymorphisme Humain population) these included: two promoter SNPs, three exonic SNPs, and a single SNP within the 3'-untranslated region. These tags were then genotyped in a rigorously phenotyped family-based collection of obese study subjects of Northern European origin. Results & conclusions: A common CNR1 haplotype (H4; prevalence 0.132) is associated with abnormal lipid homeostasis. Additional statistical tests using single tagging SNPs revealed that these associations are partly independent of body mass index.
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