title: Role of genetic variation in the cannabinoid type 1 receptor gene (CNR1) in the pathophysiology of human obesity.
abstract: 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.
authors.affiliation: Interdisciplinary Centre for Clinical Research, Medical Faculty, University of Leipzig, Leipzig, Germany.
authors.forename: Dorit
authors.initials: D
authors.lastname: Schleinitz
authors.forename: Solveig
authors.initials: S
authors.lastname: Carmienke
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Böttcher
authors.forename: Anke
authors.initials: A
authors.lastname: Tönjes
authors.forename: Janin
authors.initials: J
authors.lastname: Berndt
authors.forename: Nora
authors.initials: N
authors.lastname: Klöting
authors.forename: Beate
authors.initials: B
authors.lastname: Enigk
authors.forename: Ines
authors.initials: I
authors.lastname: Müller
authors.forename: Kerstin
authors.initials: K
authors.lastname: Dietrich
authors.forename: Jana
authors.initials: J
authors.lastname: Breitfeld
authors.forename: Gerhard H
authors.initials: GH
authors.lastname: Scholz
authors.forename: Stefan
authors.initials: S
authors.lastname: Engeli
authors.forename: Michael
authors.initials: M
authors.lastname: Stumvoll
authors.forename: Matthias
authors.initials: M
authors.lastname: Blüher
authors.forename: Peter
authors.initials: P
authors.lastname: Kovacs
mesh_terms: 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
chemical_list: D063385:Cannabinoid Receptor Modulators; D012333:RNA, Messenger; D043882:Receptors, Cannabinoid