Relation of beta 3-Adrenergic Receptor Gene Polymorphism to the Patterns of Body Fat Distribution and Insulin Sensitivity in Female Nondiabetic Offspring of Patients with NIDDM / 대한내분비학회지

ABSTRACT

BACKGROUND: Obesity is an important metabolic abnormality as a pathogenesis of non-insulin dependent diabetes mellitus(NIDDM), and genetic factors have been suggested to be involved in the development of obesity and NIDDM. beta 3-adrenergic receptor gene polymorphism has been reported to be related to an earlier onset of NIDDM and increased capacity of weight gain in obesity. The purpose of this study was to investigate the relation of beta 3-adrenergic receptor gene polymorphism to body fat distribution pattern and insulin resistance in female nondiabetic offpsring of patients with NIDDM. METHODS: We assessed the patterns of body fat distribution by anthropometric measurement, bioelectric impedence analysis and computed tomogram; insulin sensitivity by using frequently sampled intravenous glucose tolerance test and the minimal model analysis. We inverstigated the beta 3 -adrenergic receptor gene polymorphism by PCR and RFLP. RESULTS: 1) The frequency of beta 3 adrenergic receptor gene polymorphism was as follows; wild type (Trp64Trp) 69.8%, Trp64Arg heterozygote 26.4%, Arg64Arg homozygote 3.8% in the offspring of patients with NIDDM. According to obesity, there was no significant difference of distribution of Arg64 allele between nonbese and obese subjects. 2) In the mutant subjects with Arg64 allele, the concentrations of total and LDL cholesterol were significantly increased (p<0.01), but fasting serum glucose and insulin, percent body fat, visceral fat area and visceral to subcutaneous fat area ratio were insignificantly increased, SI were insiginificantly decreased. 3) Multiple regression analysis showed that Arg64 allele did not significantly associated with visceral obesity and insulin resistance. CONCLUSION: The beta 3-adrenergic receptor gene polymorphism was related to dyslipidemia, but not related to visceral adiposity or insulin resistance in nondiabetic offspring women of patients with NIDDM. Further prospective studies in these subjects will be needed for the clarification of pathogenetic role of beta 3-adrenergic receptor gene polymorphism in the development of insulin resistance and NIDDM.