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

Chun Song; 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

doi:10.1016/j.jgg.2017.11.007

Volume 45 Issue 2

Feb. 2018

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Article Navigation > Journal of Genetics and Genomics > 2018 > 45(2): 111-120

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

doi: 10.1016/j.jgg.2017.11.007

a
Laboratory of Human Population Genetics, Institute of Molecular Medicine, Peking University, Beijing 100871, China
b
State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking University, Beijing 100871, China
c
Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China
d
Laboratory of Nucleic Acid Technology, Institute of Molecular Medicine, Peking University, Beijing 100871, China
e
Human Population Genetics, Human Aging Research Institute and School of Life Sciences, Nanchang University, Nanchang 330006, China
f
Institute of Life Science and School of Life Science, Nanchang University, Nanchang 330031, China
g
School of Basic Medical Sciences, Nanchang University, Nanchang 330006, China
h
Institute of Translational Medicine, Nanchang University, Nanchang 330031, China
i
Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China

More Information

Corresponding 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.
- Type 2 diabetes,
- Glucose metabolism,
- Ubiquitination

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References(36)

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