Han Yan
Hanming Wang
Yan Zhang
Huiqing Cao
Yiqi Wan
Lingbao Kong
Shenghan Chen
Hong Xu
Bingxing Pan
Jin Zhang
Guohuang Fan
Hongbo Xin
Zicai Liang
Weiping Jia
Xiao-Li Tian
aLaboratory of Human Population Genetics, Institute of Molecular Medicine, Peking University, Beijing 100871, China
bState Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking University, Beijing 100871, China
cBeijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China
dLaboratory of Nucleic Acid Technology, Institute of Molecular Medicine, Peking University, Beijing 100871, China
eHuman Population Genetics, Human Aging Research Institute and School of Life Sciences, Nanchang University, Nanchang 330006, China
fInstitute of Life Science and School of Life Science, Nanchang University, Nanchang 330031, China
gSchool of Basic Medical Sciences, Nanchang University, Nanchang 330006, China
hInstitute of Translational Medicine, Nanchang University, Nanchang 330031, China
iShanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China
More InformationCorresponding author: E-mail address: tianxiaoli@pku.edu.cn (Xiao-Li Tian)
Received Date: 2017-09-17
Accepted Date:2017-11-25
Rev Recd Date:2017-11-23
Available Online: 2018-02-14 Publish Date:2018-02-20
Abstract
Abstract
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 ofAQR, 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.Keywords: Type 2 diabetes,
Glucose metabolism,
Ubiquitination
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