Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8644918 | Gene | 2018 | 8 Pages |
Abstract
The cAMP responsive element binding protein 1 (CREB1) is a ubiquitous transcription factor that contributes to the regulation of gluconeogenesis. The mechanisms of the CREB1 function remain largely unknown. In this study, we aimed to explore genetic variations in CREB1 promoter region and determine whether these loci affect transcriptional activity and risk on type 2 diabetes (T2D). Three polymorphisms were identified and designated as MU1, MU2 and MU3, respectively. Genotypic distribution analysis revealed that MU1 genotypes presented similar distribution between T2D and healthy controls (Pâ¯>â¯0.05), while the MU2 and MU3 showed significant differences (Pâ¯<â¯0.05). Haplotypic blocks of the three loci were constructed, and H1-TGA, H2-TTT and H3-ATT had higher frequencies in T2D patients than those in controls. Association studies revealed that the three loci significantly affected plasma glucose, glycated hemoglobin and insulin secretion. Disequilibrium analysis identified that the MU2 and MU3 variants were strongly linked in T2D (r2â¯=â¯0.348, D'â¯=â¯1.0). Further analysis indicated that MU2 (TT vs GG, ORâ¯=â¯2.38, 95%CIâ¯=â¯1.19-4.77, Pâ¯=â¯0.01) and MU3 (AA vs TT, ORâ¯=â¯1.16, 95%CIâ¯=â¯1.19-4.77, Pâ¯=â¯0.04) were significantly associated with T2D in dominant genotypes. Luciferase assay showed that T-A haplotype from the highly linked MU2 and MU3 exhibited maximal promoter activity, which was consistent with the correlation results. We concluded that the TT genotype of MU2 and the AA genotype of MU3 could be used as molecular markers for evaluating the risk on T2D.
Keywords
cAMP responsive element binding protein 1HDLCREB1OGTTZDFPICT2DSTZOral glucose tolerance testAssociationstreptozotocinExpectation MaximizationTriglyceridesType 2 diabetesType 2 diabetes mellitushigh density lipoproteinlow density lipoproteinLDLpolymorphism information contentGenome-wide association studyGWASHeterozygositySingle nucleotide polymorphismZucker Diabetic FattySNPtotal cholesterol
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Authors
Yao Xu, Ruhui Song, Wenlin Long, Hui Guo, Weilin Shi, Shiliang Yuan, Geng Xu, Tongcun Zhang,