AQR is a novel type 2 diabetes-associated gene that regulates signaling pathways critical for glucose metabolism

Publication date: Available online 14 February 2018
Source:Journal of Genetics and Genomics
Author(s): Chun Song, Han Yan, Han-Ming Wang, Yan Zhang, Huiqing Cao, Yiqi Wan, Lingbao Kong, Shenghan Chen, Hong Xu, Bing-Xing Pan, Jin Zhang, Guo-Huang Fan, Hong-Bo Xin, Zicai Liang, Weiping Jia, Xiao-Li Tian
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.



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