title: Genotype-phenotype associations in obesity dependent on definition of the obesity phenotype.
abstract: OBJECTIVE
  In previous studies of associations of variants in the genes UCP2, UCP3, PPARG2, CART, GRL, MC4R, MKKS, SHP, GHRL, and MCHR1 with obesity, we have used a case-control approach with cases defined by a threshold for BMI. In the present study, we assess the association of seven abdominal, peripheral, and overall obesity phenotypes, which were analyzed quantitatively, and thirteen candidate gene polymorphisms in these ten genes in the same cohort.
  
  
  METHODS
  Obese Caucasian men (n = 234, BMI >or= 31.0 kg/m(2)) and a randomly sampled non-obese group (n = 323), originally identified at the draft board examinations, were re-examined at median ages of 47.0 or 49.0 years by anthropometry and DEXA scanning. Obesity phenotypes included BMI, fat body mass index, waist circumference, waist for given BMI, intra-abdominal adipose tissue, hip circumference and lower body fat mass (%). Using logistic regression models, we estimated the odds for defined genotypes (dominant or recessive genetic transmission) in relation to z-scores of the phenotypes.
  
  
  RESULTS
  The minor (rare) allele for SHP 512G>C (rs6659176) was associated with increased hip circumference. The minor allele for UCP2 Ins45bp was associated with increased BMI, increased abdominal obesity, and increased hip circumference. The minor allele for UCP2 -866G>A (rs6593669) was associated with borderline increased fat body mass index. The minor allele for MCHR1 100213G>A (rs133072) was associated with reduced abdominal obesity. None of the other genotype-phenotype combinations showed appreciable associations.
  
  
  CONCLUSIONS
  If replicated in independent studies with focus on the specific phenotypes, our explorative studies suggest significant associations between some candidate gene polymorphisms and distinct obesity phenotypes, predicting beneficial and detrimental effects, depending on compartments for body fat accumulation.
authors.affiliation: Institute of Preventive Medicine, Copenhagen University Hospital, Centre for Health and Society, Copenhagen, Denmark. SI@ipm.regionh.dk
authors.forename: Sofia Inez Iqbal
authors.initials: SI
authors.lastname: Kring
authors.forename: Lesli Hingstrup
authors.initials: LH
authors.lastname: Larsen
authors.forename: Claus
authors.initials: C
authors.lastname: Holst
authors.forename: Søren
authors.initials: S
authors.lastname: Toubro
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
authors.forename: Arne
authors.initials: A
authors.lastname: Astrup
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
authors.forename: Thorkild I A
authors.initials: TI
authors.lastname: Sørensen
mesh_terms: D000328:Adult; D000483:Alleles; D050218:Body Fat Distribution; D015992:Body Mass Index; D016022:Case-Control Studies; D015331:Cohort Studies; D003718:Denmark; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D006801:Humans; D007473:Ion Channels / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics; D009765:Obesity / Q000235:genetics* / Q000503:physiopathology*; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D017481:Receptors, Somatostatin / Q000235:genetics; D000071246:Uncoupling Protein 2; D055105:Waist Circumference
chemical_list: D007473:Ion Channels; C103263:MCHR1 protein, human; D024101:Mitochondrial Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D017481:Receptors, Somatostatin; C000604389:UCP2 protein, human; D000071246:Uncoupling Protein 2; C099713:nuclear receptor subfamily 0, group B, member 2