Tesfaye M. Baye
1
, Yi Zhang
1
, Edward Smith
1
, Cecilia J. Hillard
2
, Jennifer Gunnell
1,3
,
Joel Myklebust
4
, Roland James
3,4
, Ahmed H. Kissebah
3,4
, Michael Olivier
1,4,5
, and
Russell A. Wilke
1,2,3,4
1
Human and Molecular Genetics Center,
2
Department of Pharmacology and Toxicology,
3
Department of Medicine,
4
TOPS Center for Obesity and Metabolic Research,
5
Department of Physiology, Medical College of Wisconsin; Milwaukee, Wisconsin
ABSTRACT
Since the isolation of Δ 9
-tetrahydrocannabinol (THC) from the marijuana plant in the
1960s, the mechanisms by which cannabinoids affect the human body have been the subject of considerable research efforts. In this report we investigate whether genetic variation in endocannabinoid receptor function (CNR1) is associated with anthropometric measures of human obesity and obesity-related metabolic disorders. Six tagSNPs were selected for the CNR1 gene based on HapMap: two promoter SNPs, three exonic SNPs, and a single SNP within the 3’-UTR. Under a dominant model, family-based association tests revealed significant evidence for association between CNR1 tagSNPs and obesity related traits in subjects participating in the Take Off Pounds Sensibly research program.
A common CNR1 haplotype (H4; prevalence 0.132) was associated with multiple clinical parameters used to define the metabolic syndrome, and single SNP association revealed several relationships between lipids and CNR1 that are independent of body mass index.