Genetic variation in cannabinoid receptor 1 (CNR1) is associated with derangements in lipid homeostasis, independent of body mass index
Genetic variation in cannabinoid receptor 1 (CNR1) is associated with derangements in lipid homeostasis, independent of body mass index
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DOI：
10.2217/14622416.9.11.1647
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发表时间：
2008-11-01
期刊：
影响因子：
2.1
通讯作者：
Wilke, Russell A.
中科院分区：
文献类型：
--
作者：
Baye, Tes M.;Zhang, Yi;Wilke, Russell A.
目的：在人类中，内源性大麻能信号的遗传变异与肥胖的人体测量指标有关。在随机试验中，大麻素受体1（CNR 1）受体水平的药理学阻断不仅有助于减轻体重，而且还改善了胰岛素敏感性和脂质稳态的临床指标。因此，我们检验了CNR 1的遗传变异与常见的肥胖相关代谢紊乱相关的假设。材料和方法：使用人类HapMap（Centre d 'Etude du Polymorphisme Humain population）中可用的数据，为CNR 1选择了总共六个单倍型标记SNP，这些SNP包括：两个启动子SNP、三个外显子SNP和3'非翻译区内的单个SNP。这些标签然后在严格的表型为基础的收集的北方欧洲起源的肥胖研究对象的基因分型。结果与结论：一种常见的CNR 1单倍型（H4;患病率0.132）与血脂稳态异常有关。使用单一标签SNP的其他统计测试显示，这些关联部分独立于体重指数。
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.