C825T polymorphism of the G protein beta3 subunit is associated with obesity but not with insulin sensitivity.
OBJECTIVE
The common C825T polymorphism of the gene that encodes the G protein beta3 subunit has been shown to influence lipolysis in human adipocytes and to be associated with hypertension, body fat distribution, and obesity. In addition, it has been shown to be associated with insulin resistance in a small group of hypertensive subjects. We investigated whether this polymorphism contributed to the variability in obesity in our population from southern Germany and whether it was associated with insulin sensitivity of lipolysis and/or glucose disposal.


METHODS
We determined percentage body fat, body fat distribution, glucose tolerance [oral glucose-tolerance test (OGTT)], insulin sensitivity, and serum free fatty acids using data from OGTTs (N = 774) and clamp (euglycemic hyperinsulinemic clamp, N = 216) in normal and impaired glucose tolerant subjects who were genotyped for this polymorphism.


RESULTS
Compared with noncarriers of the C825T mutation, subjects with the C825T variant (prevalence approximately 32%) had higher percentage body fat (p = 0.02) and higher BMI (p = 0.03). No conclusive effect was seen on serum free fatty acids measured either during fasting or at the end of a 2-hour OGTT. Insulin sensitivity determined during the OGTT and during the clamp, both adjusted for age, gender, and percentage body fat, was not different between the genotypes (p = 0.33 and p = 0.48, respectively).


CONCLUSIONS
We have concluded that the C825T polymorphism in the G protein beta3 subunit played an important role in the determination of obesity in this German population. However, it probably had no direct effects on insulin sensitivity of lipolysis and glucose disposal.
Stefan
Norbert
N
Department of Internal Medicine, Division of Endocrinology, Metabolism and Pathobiochemistry, University of Tübingen, Germany. norbert.stefan@med.uni-tuebingen.de
Stumvoll
Michael
M
Machicao
Fausto
F
Koch
Matthias
M
Häring
Hans U
HU
Fritsche
Andreas
A
D000273:Adipose Tissue; D000328:Adult; D000483:Alleles; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005858:Germany; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007333:Insulin Resistance / Q000235:genetics*; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D009765:Obesity / Q000235:genetics*; D011110:Polymorphism, Genetic; D021122:Protein Subunits
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; C454420:G-protein beta3 subunit; D007328:Insulin; D021122:Protein Subunits; D020962:Heterotrimeric GTP-Binding Proteins