Journal of Korean Endocrine Society 2002;17(2):236-245.
Published online April 1, 2002.
Associations of Polymorphisms in Uncoupling Protein 2 and 3-Adrenergic Receptor with Obesity in Korean Adults.
Hyejin Lee, Hyeyoung Park, Youngsun Hong, Yeon Ah Sung
Department of Internal Medicine, Ewha Womans University College of medicine, Seoul, Korea.
The genetic and environmental factors involved in the development of obesity and several candidate genes have been suggested to have an influence on energy and fuel metabolism. However, the specific genetic defects responsible for human obesity have not been identified yet. It is likely that a combination of polymorphisms in one or more candidate genes may affect energy metabolism and the development of obesity. We performed this study to determine the role of 45 bp insertion in the uncoupling protein (UCP)2 exon 8 and Trp64Arg polymorphism of beta3-adrenergic receptor ( 3-AR) gene in the regulation of body weight and the pattern of fat distribution. METHODS: In 114 subjects (male: 40, female: 74, mean body mass index: 24.1+/-2.7 kg/m2, 80 subjects with normal glucose tolerance, 34 subjects with impaired glucose tolerance), body fat distribution patterns were assessed by anthropometric measurement, bioelectric impedance analysis and computed tomogram. The genotypes of UCP genes were determined by polymerase chain reaction (PCR), and mutation in 3-AR gene by PCR followed by enzymatic digestion. RESULTS: In UCP2 genes, the frequency of deletion homozygote (DD) was 59.4%, heterozygote (DI) was 3.5% and insertion homozygote (II) was 3.1% Meanwhile, in 3-AR, the frequency of TrpTrp was 67.9%, TrpArg was 29.5% and ArgArg was 2.7%. In the lean group (subjects with a BMI less than 25 kg/m2), the frequencies of insertion allele and Arg64 allele were not significantly different than those among the overweight subjects (BMI > or = 25 kg/m2). There was not significant difference in clinical, biochemical or body fat distribution patterns between the groups according to UCP2 polymorphism. In the case of the polymorphism in 3-AR gene, the subjects with ArgArg homozygotes had lower HDL-cholesterol level (p<0.05). For the individuals over 40 years of age, BMI was greater among those with the deletion homozygotes and Arg64 allele, as compared to other groups according to the combination of UCP2 and 3-AR genotypes (p<0.05). CONCLUSION: These results suggest that genetic variations in UCP2 and 3-AR can synergistically affect metabolic rate and susceptibility to weight gain, thereby and contribute to the change in body weight in later life.
Key Words: Uncoupling protein, Beta3-adrenergic receptor, Obesity

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