权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Analysis of possible association between α-tocopherol transfer protein gene and diabetes mellitus or its clinical complications.

α-生育酚转移蛋白基因与糖尿病或其临床并发症的可能关联分析。

基本信息

批准号：
15590956
负责人：
GOTODA Takanari
金额：
$ 2.24万
依托单位：
The University of Tokyo (2004)Tokyo Women's Medical University (2003)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590956/
关键词：
vitamine E diabetes complication 遺伝子血管合併症

项目摘要

We found that serum levels of α-and γ-tocopherol were significantly decreased in patients with diabetes mellitus as compared with non-diabetic subjects. A C-to-T polymorphism in intron 4 of the human α-tocopherol transfer protein (α-TTP) gene has been shown to be associated with serum tocopherol levels (T-allele associated with lower levels). We further screened the human α-TTP gene for gene mutation or gene variant, and identified a variable number (9〜12) of adenine nucleotide repeat located 335 nucleotides upstream of the putative transcription initiation site. The allelic frequency of the -335A(n) polymorphism was as follows ; A(10)>A(11)>>A(9), A(10). Both the intron 4 C/T polymorphism and the -335A(n) polymorphism were almost in tight linkage disequilibrium, with the T-allele linked to the A(11)-allele. Luciferase promoter assay in 293 cells revealed that the reporter construct containing the A(11)-allele had significantly lower promoter activity than that containing the A(10)-allele. Among diabetic patients, the T-allele, and therefore the A(11)-allele as well, have been shown to be associated with occurrence of diabetic retinopathy [OR=1.76 (95%CI : 1.03-2.89). These results encourage further investigation about possible association between α-TTP and diabetic complications.

我们发现糖尿病患者的血清α-和γ-生育酚水平明显低于非糖尿病患者。研究表明，人α生育酚转移蛋白(α-TTP)基因内含子4的C-to-T多态与血清生育酚水平有关(T等位基因水平较低)。我们进一步筛选了人类α-TTP基因的突变或基因变异，发现在推测的转录起始点上游有一个可变数量(9~12)的腺嘌呤核苷酸重复序列。-335A(N)等位基因频率为：A(10)&gt；A(11)&gt；A(9)，A(10)。内含子4C/T多态和-335A(N)多态几乎处于紧密连锁不平衡状态，T等位基因与A(11)等位基因连锁。在293细胞中的荧光素酶启动子分析表明，含有A(11)等位基因的报告载体的启动子活性显著低于含有A(10)等位基因的报告载体。在糖尿病患者中，T等位基因以及A(11)等位基因已被证明与糖尿病视网膜病变的发生有关[OR=1.76(95%CI：1.03-2.89)]。这些结果鼓励进一步研究α-TTP与糖尿病并发症之间的可能联系。