Frequency of and interaction between polymorphisms in the beta3-adrenergic receptor and in uncoupling proteins 1 and 2 and obesity in Germans.
OBJECTIVE
To determine the role of polymorphisms in the genes for beta3-adrenergic receptor (beta3-AR) and in uncoupling proteins 1 and 2 (UCP-1, UCP-2) in obesity.


METHODS
Association study with three polymorphisms and obesity.


METHODS
Two hundred and thirty-six morbidly obese patients who underwent gastric banding surgery, 381 patients from the medical clinic and 198 healthy blood donors.


METHODS
The frequencies of the W64R in beta3-AR, the 3826A-->G in UCP-1 and the 45bp insertion in the 3 untranslated region of exon 8 in UCP-2 polymorphisms were determined.


RESULTS
There were no significant differences in the frequencies of the beta3-AR and UCP-1 polymorphisms between obese (body mass index, BMI > 30 kg/m2) and lean subjects. Lean, but not obese, carriers of the R allele of beta3-AR had a significantly higher BMI. The mean age of obese subjects (excluding diabetics) who were carriers of the G allele of the UCP-1 polymorphism, 36y, was significantly younger than wild-type, 40y (P= 0.007). This effect was not seen in lean subjects. The effect of the G allele on the mean age of obese subjects was more apparent in subjects who were also carriers of the R allele of the beta3-AR polymorphism. The frequency of the ins allele of UCP-2 was significantly higher in obese subjects, 0.31, than in lean, 0.24 (P= 0.002) and carriers of the ins allele had a significantly higher BMI, 38 vs 35 (P= 0.005). There was no association between any of the polymorphisms and type II diabetes.


CONCLUSIONS
In a German population, there was no association between the W64R in beta3-AR or the 3826A-->G in UCP-1 polymorphisms and obesity. However, they act synergistically to accelerate the development of obesity. The 45bp insertion in the 3 untranslated region of exon 8 in UCP-2 polymorphism is associated with obesity.
Evans
D
D
Medizinische Klinik, Universitätskrankenhaus Eppendorf, Hamburg, Germany. evans@uke.uni-hamburg.de
Minouchehr
S
S
Hagemann
G
G
Mann
W A
WA
Wendt
D
D
Wolf
A
A
Beisiegel
U
U
D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D015992:Body Mass Index; D002352:Carrier Proteins / Q000235:genetics*; D004247:DNA / Q000032:analysis; D005260:Female; D005787:Gene Frequency; D005858:Germany / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D007473:Ion Channels; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D024101:Mitochondrial Proteins; D009767:Obesity, Morbid / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics*; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics*; D013270:Stomach / Q000601:surgery; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2
D002352:Carrier Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D022702:Receptors, Adrenergic, beta-3; C000604371:UCP1 protein, human; C000604389:UCP2 protein, human; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D004247:DNA