Azuma N, Yoshimasa Y, Nishimura H, Yamamoto Y, Masuzaki H, Suga J, Shigemoto M, Matsuoka N, Tanaka T, Satoh N, Igaki T, Miyamoto Y, Itoh H, Yoshimasa T, Hosoda K, Nishi S, Nakao K
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Japan.
Metabolism. 1998 Apr;47(4):456-60. doi: 10.1016/s0026-0495(98)90059-2.
It has been reported that the Trp 64 Arg mutation of the human beta3-adrenergic receptor (beta3-AR) gene is related to an earlier age of onset of non-insulin-dependent diabetes mellitus (NIDDM) and features of insulin resistance and weight gain in morbidly obese patients. However, such findings have not been consistent in varying ethnic populations. In the present study, we investigated the frequency of the Trp 64 Arg mutation of the human beta3-AR gene in Japanese control subjects (n = 253) and in NIDDM (n = 314) and impaired glucose tolerance (IGT) patients (n = 100). We compared the frequency of the mutation with the body-mass index (BMI) in these groups and with the metabolic clearance rate (MCR) of glucose in the NIDDM patients. A Trp 64 Arg mutation was observed in 36.7%, 31.6%, and 37.0% of the control, NIDDM, and IGT subjects, respectively. The frequency of the homozygotes for the mutation was 4.3%, 4.8%, and 3.0%, respectively. Neither the genotype frequency (Trp/Arg, Arg/Arg) nor the frequency of the mutated allele was significantly different among the three groups. The BMI of the subjects with the mutation was not significantly higher than that of the subjects without the mutation in each group. Furthermore, the allele frequency (A) was not different among the subjects with different BMIs (BMI < 22.0, 22.0 < or = BMI < or = 26.4, BMI > 26.4) in each group. In a separate group of NIDDM patients, the MCR of the subjects with intermediate BMIs (22.0 < or = BMI < or = 26.4) with the mutation tended to be lower than that of those without the mutation. In addition, the MCR of the subjects with the mutation in this group was significantly lower compared with that of those with a BMI less than 22. These results indicate that the Trp 64 Arg mutation of the beta3-AR gene may not contribute to the development of NIDDM or be a determinant of obesity in the Japanese population. However, the mutation may contribute to insulin resistance in NIDDM patients with an intermediate BMI.
据报道，人类β3-肾上腺素能受体（β3-AR）基因的色氨酸64精氨酸突变与非胰岛素依赖型糖尿病（NIDDM）的发病年龄较早以及病态肥胖患者的胰岛素抵抗和体重增加特征有关。然而，在不同种族人群中，此类发现并不一致。在本研究中，我们调查了日本对照组受试者（n = 253）、NIDDM患者（n = 314）和糖耐量受损（IGT）患者（n = 100）中人类β3-AR基因色氨酸64精氨酸突变的频率。我们比较了这些组中突变频率与体重指数（BMI）以及NIDDM患者中葡萄糖的代谢清除率（MCR）。在对照组、NIDDM组和IGT组受试者中，分别有36.7%、31.6%和37.0%观察到色氨酸64精氨酸突变。突变纯合子的频率分别为4.3%、4.8%和3.0%。三组之间的基因型频率（色氨酸/精氨酸、精氨酸/精氨酸）和突变等位基因频率均无显著差异。每组中发生突变的受试者的BMI并不显著高于未发生突变的受试者。此外，每组中不同BMI（BMI < 22.0、22.0≤BMI≤26.4、BMI > 26.4）的受试者之间的等位基因频率（A）没有差异。在另一组NIDDM患者中，BMI处于中等水平（22.0≤BMI≤26.4）且发生突变的受试者的MCR往往低于未发生突变的受试者。此外，与BMI小于22的受试者相比，该组中发生突变的受试者的MCR显著更低。这些结果表明，β3-AR基因的色氨酸64精氨酸突变可能对日本人群中NIDDM的发生没有影响，也不是肥胖的决定因素。然而，该突变可能与BMI处于中等水平的NIDDM患者的胰岛素抵抗有关。
