Miller-Lotan Rachel, Herskowitz Yehuda, Kalet-Litman Shiri, Nakhoul Farid, Aronson Doron, Zoabi Roaa, Asaf Roy, Ben-Izhak Ofer, Sabo Edmond, Lim Sai-Kiang, Baumann Heinz, Berger Franklin G, Levy Andrew P
Technion Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Diabetes Metab Res Rev. 2005 Jul-Aug;21(4):332-7. doi: 10.1002/dmrr.556.
The human haptoglobin (Hp) gene is polymorphic with two functional classes of alleles, denoted 1 and 2. We have demonstrated in three longitudinal studies and several cross-sectional studies that the Hp genotype is an independent risk factor for diabetic vascular disease. These studies have presented a compelling argument that diabetic individuals homozygous for the Hp 1 allele are at decreased risk of vascular complications as compared to diabetic individuals with the Hp 2 allele.
The naturally occurring (wild type) mouse Hp is a class 1 Hp allele. We examined renal hypertrophy in wild-type mice, Hp knockout mice (Hp 0), and in mice with the Hp 2 allele (Hp 2) with and without diabetes.
In the absence of diabetes, we found that renal hypertrophy was significantly increased in Hp 0 mice and that this could be prevented with vitamin E. There was no difference between wild type and Hp 2 mice with regard to renal hypertrophy in the absence of diabetes. However, in the presence of diabetes, Hp 2 mice demonstrated a significant increase in renal hypertrophy as compared to wild-type mice.
These results support a direct linkage between diabetic vascular disease and the Hp genotype. These Hp-modified mice may serve as a platform on which to test a variety of pharmacological agents in order to decrease diabetic vascular disease.
人类触珠蛋白(Hp)基因具有多态性,有两种功能类型的等位基因,分别记为1和2。我们在三项纵向研究和多项横断面研究中证明,Hp基因型是糖尿病血管疾病的独立危险因素。这些研究有力地表明,与携带Hp 2等位基因的糖尿病个体相比,携带Hp 1等位基因纯合子的糖尿病个体发生血管并发症的风险降低。
天然存在的(野生型)小鼠Hp是1类Hp等位基因。我们研究了野生型小鼠、Hp基因敲除小鼠(Hp 0)以及携带Hp 2等位基因的小鼠(Hp 2)在有或无糖尿病情况下的肾肥大情况。
在无糖尿病的情况下,我们发现Hp 0小鼠的肾肥大显著增加,并且维生素E可以预防这种情况。在无糖尿病的情况下,野生型小鼠和Hp 2小鼠在肾肥大方面没有差异。然而,在有糖尿病的情况下,与野生型小鼠相比,Hp 2小鼠的肾肥大显著增加。
这些结果支持糖尿病血管疾病与Hp基因型之间存在直接联系。这些经Hp修饰的小鼠可作为一个平台,用于测试各种药物以降低糖尿病血管疾病的发生风险。