title: Polymorphism rs3123554 in CNR2 reveals gender-specific effects on body weight and affects loss of body weight and cerebral insulin action.
abstract: OBJECTIVE
  The cannabinoid-receptor system is involved in the regulation of food intake. Here, we test whether single nucleotide polymorphisms (SNPs) in CNR2, encoding the cannabinoid-receptor 2, are associated with weight in a cross-sectional cohort. Furthermore, we wanted to investigate if the identified hits influence weight loss during lifestyle intervention; and study a potential involvement of cerebral insulin action.
  
  
  METHODS
  2006 subjects at increased risk for type 2 diabetes mellitus were genotyped for 5 tagging SNPs in the CNR2 locus. All subjects underwent a 75-g OGTT. 345 subjects participated in a lifestyle intervention (TUebingen Lifestyle Intervention Programme). Cerebrocortical insulin sensitivity was measured by magnetoencephalography after intranasal insulin application in 43 subjects.
  
  
  RESULTS
  In the cross-sectional cohort, the minor allele of rs3123554 was associated with lower BMI (Padd = 0.01, Prec = 0.004), and this was attributable to its effect in women only. Interestingly, during lifestyle intervention, carriers of the same allele lost less body weight (Padd = 0.03, Prec = 0.008). Moreover, carriers of this minor allele showed lower cerebral insulin sensitivity (Prec = 0.0402).
  
  
  CONCLUSIONS
  The minor allele of rs3123554 is associated cross-sectionally with lower body weight, whereas during intervention the same allele led to less reduction of body weight. Reduced cerebral insulin sensitivity in carriers of this allele might contribute to these disadvantageous effects during lifestyle intervention.
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology, and Clinical Chemistry, Eberhard Karls University, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen (Paul Langerhans Institute Tübingen), Tübingen, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Ketterer
authors.forename: Martin
authors.initials: M
authors.lastname: Heni
authors.forename: Krunoslav
authors.initials: K
authors.lastname: Stingl
authors.forename: Otto
authors.initials: O
authors.lastname: Tschritter
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Linder
authors.forename: Robert
authors.initials: R
authors.lastname: Wagner
authors.forename: Fausto
authors.initials: F
authors.lastname: Machicao
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Häring
authors.forename: Hubert
authors.initials: H
authors.lastname: Preissl
authors.forename: Harald
authors.initials: H
authors.lastname: Staiger
authors.forename: Andreas
authors.initials: A
authors.lastname: Fritsche
mesh_terms: D000273:Adipose Tissue / Q000737:chemistry; D000281:Administration, Intranasal; D000483:Alleles; D015992:Body Mass Index; D054022:Cerebrum / Q000502:physiology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D030541:Databases, Genetic; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D017097:Electric Impedance; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000502:physiology; D007333:Insulin Resistance; D008019:Life Style; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D020641:Polymorphism, Single Nucleotide; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics*; D012727:Sex Characteristics; D015431:Weight Loss / Q000235:genetics*
chemical_list: C588309:CNR2 protein, human; D007328:Insulin; D043885:Receptor, Cannabinoid, CB2