Open AccessC825T Polymorphism of the G Protein β 3 Subunit Is Associated with Obesity but Not with Insulin Sensitivity
Author(s) -
Stefan Norbert,
Stumvoll Michael,
Machicao Fausto,
Koch Matthias,
Häring Hans U.,
Fritsche Andreas
Publication year - 2004
Publication title -
obesity research
Language(s) - English
Resource type - Journals
eISSN - 1550-8528
pISSN - 1071-7323
DOI - 10.1038/oby.2004.78
Subject(s) - medicine , endocrinology , lipolysis , insulin resistance , obesity , insulin , polymorphism (computer science) , population , type 2 diabetes , diabetes mellitus , genotype , adipose tissue , biology , gene , genetics , environmental health
Objective : The common C825T polymorphism of the gene that encodes the G protein β 3 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. Research Methods and Procedures : 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 ∼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). Discussion : We have concluded that the C825T polymorphism in the G protein β 3 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.