Genetic variation in cannabinoid receptor 1 (CNR1) is associated with derangements in lipid homeostasis, independent of body mass index.
OBJECTIVE
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.


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.


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.
Baye
Tes M
TM
Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Zhang
Yi
Y
Smith
Edward
E
Hillard
Cecilia J
CJ
Gunnell
Jennifer
J
Myklebust
Joel
J
James
Roland
R
Kissebah
Ahmed H
AH
Olivier
Michael
M
Wilke
Russell A
RA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D015331:Cohort Studies; D050171:Dyslipidemias / Q000097:blood / Q000235:genetics*; D006239:Haplotypes; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008055:Lipids / Q000097:blood; D008875:Middle Aged; D009679:Nuclear Family; D009765:Obesity / Q000097:blood / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D019655:Quantitative Trait, Heritable; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics*; D055815:Young Adult
D008055:Lipids; D043884:Receptor, Cannabinoid, CB1