Oksanen L, Mustajoki P, Kaprio J, Kainulainen K, Jänne O, Peltonen L, Kontula K
Department of Medicine, University of Helsinki, Finland.
Int J Obes Relat Metab Disord. 1996 Dec;20(12):1055-61.
The Trp64-->Arg allele of the beta 3-adrenergic receptor gene was recently proposed to be associated with an earlier onset of non-insulin-dependent diabetes mellitus (NIDDM), features of insulin resistance and a tendency to gain weight. We investigated whether the Arg64 allele predisposes to severe obesity.
A genetic association study of 254 subjects with morbid obesity [body-mass index (BMI) > or = 40; mean 42.8 +/- 7.0] and 151 lean healthy control subjects [BMI < or = 25; mean BMI 22.3 +/- 1.9].
beta 3-adrenergic receptor genotyping was carried out with a solid-phase minisequencing technique. Serum lipids, glucose and insulin levels in the obese subjects were also determined.
The frequency of the Arg64 did not significantly differ in the morbidly obese patients (9.1%) and lean controls (8.9%), nor was there any statistically significant association between the mean BMI values and the beta 3-adrenergic receptor genotype. However, obese subjects carrying the Arg64 allele developed obesity more often before the age of 15 y than those without it (P < 0.05, adjusted for multiple comparisons). The frequency of the Arg64 allele was similar in nondiabetic and diabetic patients; the mean age at the onset of NIDDM did not differ according to the beta 3-adrenergic receptor genotype. There was no significant association between the receptor genotype and the level of the serum cholesterol, HDL-cholesterol, triglyceride, glucose or insulin, nor was this polymorphism associated with the behavioural or psychopathological characteristics of the morbidly obese subjects. Response to a 16 w treatment program including a very-low calorie diet (VLCD) regimen, dietary and exercise counseling, as well as behavioural modifications, did not differ according to the genotype.
Our data do not support a significant role for the codon 64 polymorphism of the beta 3-adrenergic receptor as a genetic marker of morbid obesity. Although there was an association between the Arg64 allele and an earlier onset of obesity in individuals subsequently developing morbid obesity, this allele was not associated with the actual BMI gained or response to weight-loss therapy on a hypocaloric diet.
β3 - 肾上腺素能受体基因的色氨酸64位密码子突变为精氨酸的等位基因（Trp64→Arg）最近被认为与非胰岛素依赖型糖尿病（NIDDM）的较早发病、胰岛素抵抗特征以及体重增加倾向有关。我们研究了精氨酸64位等位基因（Arg64）是否易导致严重肥胖。
对254例病态肥胖患者[体重指数（BMI）≥40；平均42.8±7.0]和151例健康瘦人对照者[BMI≤25；平均BMI 22.3±1.9]进行基因关联研究。
采用固相微测序技术进行β3 - 肾上腺素能受体基因分型。同时测定肥胖患者的血脂、血糖和胰岛素水平。
病态肥胖患者（9.1%）和瘦人对照者（8.9%）中Arg64等位基因频率无显著差异，BMI均值与β3 - 肾上腺素能受体基因型之间也无统计学显著关联。然而，携带Arg64等位基因的肥胖患者在15岁前发生肥胖的频率高于未携带该等位基因者（P<0.05，经多重比较校正）。非糖尿病患者和糖尿病患者中Arg64等位基因频率相似；NIDDM发病的平均年龄根据β3 - 肾上腺素能受体基因型无差异。受体基因型与血清胆固醇、高密度脂蛋白胆固醇、甘油三酯、血糖或胰岛素水平之间无显著关联，该多态性也与病态肥胖患者的行为或精神病理特征无关。对包括极低热量饮食（VLCD）方案、饮食和运动咨询以及行为改变的16周治疗方案的反应，根据基因型无差异。
我们的数据不支持β3 - 肾上腺素能受体64位密码子多态性作为病态肥胖遗传标志物的重要作用。虽然Arg64等位基因与随后发生病态肥胖个体的肥胖较早发病有关，但该等位基因与实际增加的BMI或低热量饮食减肥治疗的反应无关。
