A functional polymorphism of the TNF-α gene that is associated with type 2 DM
- 作者：Shinji Susa ; Makoto Daimon ; Jun-Ichi Sakabe ; Hidenori Sato ; Toshihide Oizumi ; Shigeru Karasawa ; Kiriko Wada ; Yumi Jimbu ; Wataru Kameda ; Mitsuru Emi ; Masaaki Muramatsu ; Takeo Kato
- 关键词：TNF-
src="http ; //www.sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0"> ; Functional SNP ; Allele-specific binding ; Allele-specific transcriptional activity ; YY-1 ; Funagata study
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2008
- 期刊代码：159_0006291x
- 类别：bio
- 出版时间：9 May 2008
- 卷：369
- 期：3
- 页码：943-947
- 文件大小：656 K
摘要
To examine the association of the tumor necrosis factor-![]()
src="http://www.sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0"> (TNF-![]()
src="http://www.sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">) gene region with type 2 diabetes (DM), 11 single-nucleotide polymorphisms (SNPs) of the region were analyzed. The initial study using a sample set (148 cases vs. 227 controls) showed a significant association of the SNP IVS1G + 123A of the TNF-![]()
src="http://www.sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0"> gene with DM (p = 0.0056). Multiple logistic regression analysis using an enlarged sample set (225 vs. 716) revealed the significant association of the SNP with DM independently of any clinical traits examined (OR: 1.49, p = 0.014). The functional relevance of the SNP were examined by the electrophoretic mobility shift assays using nuclear extracts from the U937 and NIH3T3 cells and luciferase assays in these cells with Simian virus 40 promoter- and TNF-![]()
src="http://www.sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0"> promoter–reporter gene constructs. The functional analyses showed that YY1 transcription factor bound allele-specifically to the SNP region and, the IVS1 + 123A allele had an increase in luciferase expression compared with the G allele.