Mori H, Ikegami H, Kawaguchi Y, Seino S, Yokoi N, Takeda J, Inoue I, Seino Y, Yasuda K, Hanafusa T, Yamagata K, Awata T, Kadowaki T, Hara K, Yamada N, Gotoda T, Iwasaki N, Iwamoto Y, Sanke T, Nanjo K, Oka Y, Matsutani A, Maeda E, Kasuga M
Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
Diabetes. 2001 Apr;50(4):891-4. doi: 10.2337/diabetes.50.4.891.
The allele frequencies for a Pro12-->Ala substitution in peroxisome proliferator-activated receptor-gamma differ among ethnic groups, and its relationship with diabetes and associated diseases is controversial. The prevalence of this polymorphism and its effects on clinical characteristics have now been evaluated with a large number of Japanese individuals with type 2 diabetes (n = 2,201) and normal control subjects (n = 1,212) recruited by 10 institutions located in seven different cities in Japan. The allele frequency for the Ala12 variant was significantly lower in the type 2 diabetic group than in the control group (2.39 vs. 4.13%, P = 0.000054). However, compared with subjects without the Ala12 variant, the diabetic subjects with this variant exhibited a significantly higher serum concentration of total cholesterol (P = 0.001), manifested a reduced capacity for insulin secretion as evaluated by homeostasis model assessment (P = 0.007), and tended to possess a higher level of HbA1c. These data suggest that the Ala12 variant is associated with a reduced risk for the development of diabetes in the general population, but that it may be also a risk factor for insulin deficiency and disease severity in individuals with type 2 diabetes.
过氧化物酶体增殖物激活受体γ（PPAR-γ）基因Pro12→Ala替代的等位基因频率在不同种族群体中存在差异，并且其与糖尿病及相关疾病的关系也存在争议。目前，通过日本七个不同城市的10家机构招募的大量2型糖尿病患者（n = 2201）和正常对照者（n = 1212），对该多态性的患病率及其对临床特征的影响进行了评估。2型糖尿病组中Ala12变体的等位基因频率显著低于对照组（2.39%对4.13%，P = 0.000054）。然而，与没有Ala12变体的受试者相比，具有该变体的糖尿病受试者表现出显著更高的血清总胆固醇浓度（P = 0.001），通过稳态模型评估显示胰岛素分泌能力降低（P = 0.007），并且倾向于具有更高水平的糖化血红蛋白（HbA1c）。这些数据表明，Ala12变体在普通人群中与糖尿病发生风险降低相关，但在2型糖尿病患者中它也可能是胰岛素缺乏和疾病严重程度的一个危险因素。
