AQR is a novel type 2 diabetes-associated gene that regulates signaling pathways critical for glucose metabolism
| Autor: | Bing-Xing Pan, Han Yan, Yiqi Wan, Weiping Jia, Xiao-Li Tian, Hong Xu, Shenghan Chen, Zicai Liang, Huiqing Cao, Hanming Wang, Guohuang Fan, Jin Zhang, Chun Song, Hongbo Xin, Lingbao Kong, Yan Zhang |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Genotype endocrine system diseases Glucose uptake Biology Polymorphism Single Nucleotide 03 medical and health sciences 0302 clinical medicine PCK2 Genetics Humans Genetic Predisposition to Disease Molecular Biology PI3K/AKT/mTOR pathway Gene knockdown Glycogen Synthase Kinase 3 beta TOR Serine-Threonine Kinases nutritional and metabolic diseases Type 2 Diabetes Mellitus Hep G2 Cells Protein ubiquitination Cell biology Glucose 030104 developmental biology Diabetes Mellitus Type 2 Phosphorylation Signal transduction Phosphoenolpyruvate Carboxykinase (ATP) RNA Helicases 030217 neurology & neurosurgery Genome-Wide Association Study |
| Zdroj: | Journal of Genetics and Genomics. 45:111-120 |
| ISSN: | 1673-8527 |
| DOI: | 10.1016/j.jgg.2017.11.007 |
| Popis: | Type 2 diabetes mellitus (T2DM) is a common metabolic disease influenced by both genetic and environmental factors. In this study, we performed an in-house genotyping and meta-analysis study using three independent GWAS datasets of T2DM and found that rs3743121, located 1 kb downstream of AQR, was a novel susceptibility SNP associated with T2DM. The risk allele C of rs3743121 was correlated with the increased expression of AQR in white blood cells, similar to that observed in T2DM models. The knockdown of AQR in HepG2 facilitated the glucose uptake, decreased the expression level of PCK2, increased the phosphorylation of GSK-3β, and restored the insulin sensitivity. Furthermore, the suppression of AQR inhibited the mTOR pathway and the protein ubiquitination process. Our study suggests that AQR is a novel type 2 diabetes-associated gene that regulates signaling pathways critical for glucose metabolism. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect