Wenyi Z, Suzuki S, Hirai M, Hinokio Y, Tanizawa Y, Matsutani A, Satoh J, Oka Y
Division of Molecular Metabolism and Diabetes, Department of Internal Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.
Diabetologia. 2003 Jul;46(7):972-6. doi: 10.1007/s00125-003-1145-1. Epub 2003 Jun 27.
AIM/HYPOTHESIS: Urotensin II is a potent vasoactive hormone and the urotensin II gene (UTS2) is localized to 1p36-p32, one of the regions reported to show possible linkage with Type 2 diabetes in Japanese subjects. The aim of this study is to investigate a possible contribution of SNPs in the UTS2 gene to the development of Type 2 diabetes.
We surveyed SNPs in the UTS2 gene in 152 Japanese subjects with Type 2 diabetes mellitus and two control Japanese cohorts: one consisting of 122 elderly subjects who met stringent criteria for being non-diabetic, including being older than 60 years of age with no evidence of diabetes (HbA(1c)<5.6%), and another 268 subjects with normal glucose tolerance.
We identified two SNPs with amino acid substitutions, designated T21M and S89N. The allele frequency of 89N was higher in Type 2 diabetic patients than in both elderly normal subjects (p=0.0018) and subjects with normal glucose tolerance (p=0.0011), whereas the allele frequency of T21M was essentially identical in these three groups. Furthermore, in the subjects with normal glucose tolerance, 89N was associated with higher insulin concentrations on oral glucose tolerance test, suggesting reduced insulin sensitivity in subjects with 89N.
CONCLUSION/INTERPRETATION: These results strongly suggest that the S89N polymorphism in the UTS2 gene is associated with the development of Type 2 diabetes, via insulin sensitivity, in Japanese subjects.
目的/假设：尾加压素II是一种强效血管活性激素，尾加压素II基因（UTS2）定位于1p36 - p32，该区域据报道在日本人群中可能与2型糖尿病存在连锁关系。本研究的目的是调查UTS2基因中的单核苷酸多态性（SNP）对2型糖尿病发生发展的可能作用。
我们在152名日本2型糖尿病患者以及两个日本对照队列中调查了UTS2基因中的SNP：一个队列由122名符合严格非糖尿病标准的老年受试者组成，包括年龄大于60岁且无糖尿病证据（糖化血红蛋白（HbA1c）<5.6%），另一个队列由268名糖耐量正常的受试者组成。
我们鉴定出两个有氨基酸替换的SNP，分别命名为T21M和S89N。2型糖尿病患者中89N的等位基因频率高于老年正常受试者（p = 0.0018）和糖耐量正常的受试者（p = 0.0011），而T21M的等位基因频率在这三组中基本相同。此外，在糖耐量正常的受试者中，89N与口服葡萄糖耐量试验中较高的胰岛素浓度相关，提示携带89N的受试者胰岛素敏感性降低。
结论/解读：这些结果强烈表明，在日本人群中，UTS2基因中的S89N多态性通过胰岛素敏感性与2型糖尿病的发生有关。
