Genotype-phenotype associations in obesity dependent on definition of the obesity phenotype.
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.
Kring
Sofia Inez Iqbal
SI
Institute of Preventive Medicine, Copenhagen University Hospital, Centre for Health and Society, Copenhagen, Denmark. SI@ipm.regionh.dk
Larsen
Lesli Hingstrup
LH
Holst
Claus
C
Toubro
Søren
S
Hansen
Torben
T
Astrup
Arne
A
Pedersen
Oluf
O
Sørensen
Thorkild I A
TI
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
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