Role of genetic variation in the cannabinoid type 1 receptor gene (CNR1) in the pathophysiology of human obesity.
OBJECTIVE
The endocannabinoid system may contribute to the association of visceral fat accumulation with metabolic diseases. Here we investigated the effects of genetic variation in the cannabinoid type 1 receptor gene (CNR1) on its mRNA expression in adipose tissue from visceral and subcutaneous depots and on the development of obesity.


METHODS
CNR1 was sequenced in 48 nonrelated German Caucasians to detect genetic variation. Five representative variants including HapMap tagging SNPs (rs12720071, rs806368, rs806370, rs1049353 and rs806369) were genotyped for subsequent association studies in two independent cohorts (total n = 2774) with detailed metabolic testing: subjects from the Leipzig Study (n = 1857) and a self-contained population of Sorbs from Germany (n = 917).


RESULTS
In a case-control study of lean (BMI <25 kg/m(2)) versus obese (BMI >30 kg/m(2)) subjects, rs806368 was found to be nominally associated with obesity in the Sorbian cohort (adjusted p < 0.05), but not in the Leipzig cohort. Also, several SNPs (rs806368, rs806370 and rs12720071) were nominally associated with serum leptin levels (p < 0.05 after adjusting for age, sex and BMI). However, none of these associations remained significant after accounting for multiple testing. Furthermore, none of the SNPs were related to CNR1 mRNA expression in visceral and subcutaneous fat.


CONCLUSIONS
The data suggest that common genetic variation in the CNR1 gene does not influence mRNA expression in adipose tissue nor does it play a significant role in the pathophysiology of obesity in German and Sorbian populations.
Schleinitz
Dorit
D
Interdisciplinary Centre for Clinical Research, Medical Faculty, University of Leipzig, Leipzig, Germany.
Carmienke
Solveig
S
Böttcher
Yvonne
Y
Tönjes
Anke
A
Berndt
Janin
J
Klöting
Nora
N
Enigk
Beate
B
Müller
Ines
I
Dietrich
Kerstin
K
Breitfeld
Jana
J
Scholz
Gerhard H
GH
Engeli
Stefan
S
Stumvoll
Michael
M
Blüher
Matthias
M
Kovacs
Peter
P
D000273:Adipose Tissue / Q000378:metabolism / Q000502:physiology; D063385:Cannabinoid Receptor Modulators / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D016022:Case-Control Studies; D015870:Gene Expression; D005796:Genes; D014644:Genetic Variation; D005838:Genotype; D005858:Germany; D006801:Humans; D050152:Intra-Abdominal Fat / Q000378:metabolism; D009765:Obesity / Q000235:genetics* / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043882:Receptors, Cannabinoid / Q000235:genetics / Q000378:metabolism; D050151:Subcutaneous Fat / Q000378:metabolism; D044465:White People / Q000235:genetics
D063385:Cannabinoid Receptor Modulators; D012333:RNA, Messenger; D043882:Receptors, Cannabinoid