A functional polymorphism of the TNF-{alpha} gene that is associated with type 2 DM
- Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585 (Japan)
- HuBit Genomix Research Institute, Tokyo 102-0092 (Japan)
To examine the association of the tumor necrosis factor-{alpha} (TNF-{alpha}) 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-{alpha} 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-{alpha} 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.
- OSTI ID:
- 21143670
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 369, Issue 3; Other Information: DOI: 10.1016/j.bbrc.2008.02.121; PII: S0006-291X(08)00411-7; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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