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Genetic variation in cannabinoid receptor 1 (CNR1) is associated with derangements in lipid homeostasis, independent of body mass index. Pharmacogenomics 2008 Nov;9(11):1647-56

Date

11/21/2008

Pubmed ID

19018721

Pubmed Central ID

PMC2784739

DOI

10.2217/14622416.9.11.1647

Scopus ID

2-s2.0-61549101858 (requires institutional sign-in at Scopus site)   45 Citations

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.

Author List

Baye TM, Zhang Y, Smith E, Hillard CJ, Gunnell J, Myklebust J, James R, Kissebah AH, Olivier M, Wilke RA

Author

Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Aged
Aged, 80 and over
Body Mass Index
Cohort Studies
Dyslipidemias
Haplotypes
Homeostasis
Humans
Insulin Resistance
Lipids
Middle Aged
Nuclear Family
Obesity
Polymorphism, Single Nucleotide
Quantitative Trait, Heritable
Receptor, Cannabinoid, CB1
Young Adult