Højlund K, Christiansen C, Bjørnsbo K S, Poulsen P, Bathum L, Henriksen J E, Lammert O, Beck-Nielsen H
Diabetes Research Centre, Department of Endocrinology, Odense University Hospital, Odense, Denmark.
Diabetes Obes Metab. 2006 May;8(3):322-30. doi: 10.1111/j.1463-1326.2005.00509.x.
The tryptophan to arginine change in position 64 (Trp64Arg) polymorphism of the beta3-adrenergic receptor (beta3AR) gene has been associated with an increased prevalence of obesity, insulin resistance and type 2 diabetes. In this, decreased rates of energy expenditure and impaired insulin secretion could play a role.
In 10 male twin pairs discordant for the Trp64Arg polymorphism, we examined insulin response to glucose by an oral glucose tolerance test (OGTT), a frequently sampled intravenous glucose tolerance test (FSIGT), body composition by the bioimpedance method, dual-energy X-ray absorptiometry scanning and energy expenditure by indirect and direct calorimetry.
Twins heterozygous for the Trp64Arg polymorphism showed significantly lower fat mass independent of the method used, and significantly lower fasting insulin and glucose concentrations compared with their homozygous wild-type co-twins. Correspondingly, insulin resistance and insulin secretion determined by homeostasis model assessment were significantly lower in twins carrying the Trp64Arg polymorphism. However, there were no significant differences in adiponectin levels, insulinogenic index assessed by OGTT, or insulin sensitivity, acute insulin response to glucose, glucose effectiveness or insulin disposition index assessed by minimal modelling of the FSIGT. Furthermore, there were no differences in sleeping, resting or post-prandial energy expenditure.
In male twins with a high similarity in genetic and environmental background, the Trp64Arg polymorphism of the beta3AR gene is associated with lower fat mass, fasting insulin levels and an appropriate insulin response to glucose. Thus, heterozygosity for the Trp64Arg variant is unlikely to increase the risk of obesity, insulin resistance or type 2 diabetes.
β3-肾上腺素能受体（β3AR）基因第64位密码子色氨酸突变为精氨酸（Trp64Arg）的多态性与肥胖、胰岛素抵抗及2型糖尿病患病率增加有关。其中，能量消耗率降低和胰岛素分泌受损可能起了作用。
在10对Trp64Arg多态性不一致的男性双胞胎中，我们通过口服葡萄糖耐量试验（OGTT）、频繁采样静脉葡萄糖耐量试验（FSIGT）检测胰岛素对葡萄糖的反应，采用生物电阻抗法、双能X线吸收法扫描检测身体成分，并通过间接和直接量热法检测能量消耗。
与纯合野生型双胞胎相比，Trp64Arg多态性杂合的双胞胎无论采用何种方法检测，脂肪量均显著降低，空腹胰岛素和葡萄糖浓度也显著降低。相应地，采用稳态模型评估法测定，携带Trp64Arg多态性的双胞胎胰岛素抵抗和胰岛素分泌显著降低。然而，脂联素水平、通过OGTT评估的胰岛素生成指数，或通过FSIGT最小模型评估的胰岛素敏感性、对葡萄糖的急性胰岛素反应、葡萄糖效能或胰岛素处置指数均无显著差异。此外，睡眠、静息或餐后能量消耗也无差异。
在遗传和环境背景高度相似的男性双胞胎中，β3AR基因的Trp64Arg多态性与较低的脂肪量、空腹胰岛素水平及对葡萄糖的适当胰岛素反应相关。因此，Trp64Arg变异体的杂合性不太可能增加肥胖、胰岛素抵抗或2型糖尿病的风险。
