The C825T gene polymorphism, a substitution of cytosine (C) for thymine (T) at the nucleotide 825 of G-protein β3 subunit (GNB3) cDNA, activates a cryptic splice site that results in alternative splicing of exon 9, leading to deletion of 41 amino acids in the β3 subunit of GTP-binding proteins. In cross-sectional human studies, the 825T allele of the GNB3 polymorphism has been associated with hypertension and obesity in black Africans and Caucasians. PURPOSE: The purpose of the present study was to investigate whether the GNB3 genotypes modulated the effect of a 12-wk aerobic exercise program on obesity indices, cardiopulmonary fitness, and metabolic syndrome markers in mid-life Korean women. METHODS: A total of 51 abdominally obese women (waist circumference >80cm) aged 45–65 yrs were invited to participate in this study. Following an overnight fast, obesity indices (i.e., body mass index, percent body fat, waist circumference), cardiopulmonary fitness was determined during the treadmill exercise testing. Fasting glucose and lipoprotein-lipids (TC, HDLC, LDLC, TG), leptin, adiponectin were determined by using the commercial analysis kits. A 75 g of oral glucose tolerance test (OGTT) were peformed by using the standardized procedure. Then, all the subjects participated in a dance sports program for 12 weeks (2 hrs/day, 3 times/week). Following the dance sports program, the same measurements performed at the baseline were conducted. RESULTS: Two-way ANOVA analyses showed that the 12-wk aerobic exercise program resulted in significant improvements in all the measured variables (time effects only) except for SBP, DBP, and TC, while the degrees of the improvements were not dependent upon the GNB3 genotypes (no significant time by genotype interaction). However, both the CT heterozygotes and CC homozygotes tended to have greater reductions in area under curve during the OGTT than the TT homozygotes. Conclusions:The current findings suggest that the degree to which exercise training improves insulin sensitivity (i.e., improved glucose tolerance) may be partially modulated by the GNB3 genotype.