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Genetic variation in cannabinoid receptor 1 (CNR1) is associated with derangements in lipid homeostasis, independent of body mass index
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Baye, Tes M., Zhang, Yi, Smith, Edward M., Hillard, Cecilia J., Gunnell, Jennifer, Myklebust, Joel, James, Roland, Kissebah, Ahmed, Olivier, M. (Michael) and Wilke, Russell A. (2008) Genetic variation in cannabinoid receptor 1 (CNR1) is associated with derangements in lipid homeostasis, independent of body mass index. Pharmacogenomics, Vol.9 (No.11). pp. 1647-1656. doi:10.2217/14622416.9.11.1647 ISSN 1462-2416.
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Official URL: http://dx.doi.org/10.2217/14622416.9.11.1647
Abstract
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.
| Item Type: | Journal Article | ||||
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| Subjects: | Q Science > QH Natural history > QH426 Genetics Q Science > QP Physiology |
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| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) > Biological Sciences ( -2010) Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) |
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| Library of Congress Subject Headings (LCSH): | Genomics, Human genetics -- Variation -- Europe, Northern, Genetics -- Research, High density lipoproteins, Low density lipoproteins, Obesity, Triglycerides | ||||
| Journal or Publication Title: | Pharmacogenomics | ||||
| Publisher: | Future Medicine Ltd. | ||||
| ISSN: | 1462-2416 | ||||
| Official Date: | 2008 | ||||
| Dates: |
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| Volume: | Vol.9 | ||||
| Number: | No.11 | ||||
| Page Range: | pp. 1647-1656 | ||||
| DOI: | 10.2217/14622416.9.11.1647 | ||||
| Status: | Peer Reviewed |
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