A functional polymorphism of the TNF-alpha gene that is associated with type 2 DM.
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.
Susa
Shinji
S
Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.
Daimon
Makoto
M
Sakabe
Jun-Ichi
J
Sato
Hidenori
H
Oizumi
Toshihide
T
Karasawa
Shigeru
S
Wada
Kiriko
K
Jimbu
Yumi
Y
Kameda
Wataru
W
Emi
Mitsuru
M
Muramatsu
Masaaki
M
Kato
Takeo
T
D000368:Aged; D000483:Alleles; D000818:Animals; D044466:Asian People / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D007564:Japan; D008156:Luciferases / Q000235:genetics; D008297:Male; D051379:Mice; D008875:Middle Aged; D041681:NIH 3T3 Cells; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D050986:YY1 Transcription Factor / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha; D050986:YY1 Transcription Factor; D008156:Luciferases