Antizyme inhibitor 1 genetic polymorphisms associated with diabetic patients validated in the livers of diabetic mice

Cheng-Hsu Chen; Yeh-Han Wang; Shang-Feng Tsai; Tung-Min Yu; Shih-Yin Chen; Fuu-Jen Tsai

doi:10.3892/etm.2019.7919

Antizyme inhibitor 1 genetic polymorphisms associated with diabetic patients validated in the livers of diabetic mice

Exp Ther Med. 2019 Oct;18(4):3139-3146. doi: 10.3892/etm.2019.7919. Epub 2019 Aug 20.

Authors

Cheng-Hsu Chen^{1

2

3

4}, Yeh-Han Wang⁵, Shang-Feng Tsai^{2

3

6}, Tung-Min Yu^{2

4}, Shih-Yin Chen^{7

8}, Fuu-Jen Tsai^{7

8

9}

Affiliations

¹ Department of Medical Research, Division of Basic Medical Sciences, Taichung Veterans General Hospital, Taichung 40705, Taiwan, R.O.C.
² Department of Internal Medicine, Division of Nephrology, Taichung Veterans General Hospital, Taichung 40705, Taiwan, R.O.C.
³ Department of Life Science, Tunghai University, Taichung 40705, Taiwan, R.O.C.
⁴ School of Medicine, China Medical University, Taichung 40402, Taiwan, R.O.C.
⁵ Department of Anatomical Pathology, Taipei Institute of Pathology, School of Medicine, National Yang-Ming University, 11221 Taipei, Taiwan, R.O.C.
⁶ Department of Internal Medicine, School of Medicine, National Yang-Ming University, 11221 Taipei, Taiwan, R.O.C.
⁷ School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan, R.O.C.
⁸ Genetics Center, Medical Research, China Medical University Hospital, Taichung 40447, Taiwan, R.O.C.
⁹ Department of Medical Genetics, China Medical University Hospital, Taichung 40447, Taiwan, R.O.C.

Abstract

Diabetes mellitus (DM) is a complex disease caused by absolute or relative insulin deficiency. The C57BLKsJ-db/db mouse model is a useful animal model for studying type 2 DM (T2DM). The present study investigated the association between an antizyme inhibitor 1 (AZIN1) gene polymorphism (rs1062048) and T2DM susceptibility in 2,270 Taiwanese individuals (570 patients with T2DM and 1,700 controls). Additionally, the present study investigated AZIN1 gene and protein expression in the liver tissues of mice in three age groups (4, 16 and 32 weeks) through reverse transcription-quantitative PCR, western blotting and immunohistochemistry. The data indicated that the genotype frequency distribution of the rs1062048 single-nucleotide polymorphism differed significantly between the patients with T2DM and controls (P<0.05). Furthermore, gene and protein expression levels of AZIN1 were significantly lower in early stage and late stage T2DM mouse liver samples than in control samples. Overall, the data suggested that AZIN1 expression is involved in T2DM development.

Keywords: C57BLKsJ-db/db mouse; antizyme inhibitor 1; type 2 diabetes mellitus.