Research Papers:
Pharmacogenetics of dipeptidyl peptidase 4 inhibitors in a Taiwanese population with type 2 diabetes
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Abstract
Wen-Ling Liao1,2,*, Wen-Jane Lee3,*, Ching-Chu Chen4,5,*, Chieh Hsiang Lu6,7,8,*, Chien-Hsiun Chen5,9, Yi-Chun Chou9, I-Te Lee10,11,12, Wayne H-H Sheu10,12,13,14, Jer-Yuarn Wu5,9, Chi-Fan Yang9, Chung-Hsing Wang15,16, Fuu-Jen Tsai5,17,18
1Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan
2Center for Personalized Medicine, China Medical University Hospital, Taichung, Taiwan
3Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
4Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, Taichung, Taiwan
5School of Chinese Medicine, China Medical University, Taichung, Taiwan
6Department of Internal Medicine, Ditmanson Medical Foundation, Chiayi Christian Hospital, Chiayi City, Taiwan
7Department of Nursing, College of Nursing and Health Sciences, DAYEH University, Changhua, Taiwan
8Department of Business management, College of Management, National Chung Cheng University, Chia-yi, Taiwan
9National Center for Genome Medicine, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
10Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans Hospital, Taichung, Taiwan
11School of Medicine, Chung Shan Medical University, Taichung, Taiwan
12School of Medicine, National Yang-Ming University, Taipei, Taiwan
13School of Medicine, National Defense Medical Center, Taipei, Taiwan
14Institute of Medical Technology, National Chung-Hsing University, Taichung, Taiwan
15Department of Genetics and Metabolism, Children’s Hospital of China Medical University, Taichung, Taiwan
16School of Medicine, China Medical University, Taichung, Taiwan
17Department of Medical Genetics, China Medical University Hospital, Taichung, Taiwan
18Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan
*These authors have contributed equally to this work
Correspondence to:
Fuu-Jen Tsai, email: [email protected]
Keywords: DPP-4 inhibitors, pharmacogenetics, Taiwanese, type 2 diabetes
Received: January 29, 2016 Accepted: January 03, 2017 Published: February 01, 2017
ABSTRACT
Dipeptidyl peptidase-4 (DPP-4) inhibitors are oral anti-hyperglycemic drugs enabling effective glycemic control in type 2 diabetes (T2D). Despite DPP-4 inhibitors’ advantages, the patients’ therapeutic response varies. In this retrospective cohort study, 171 Taiwanese patients with T2D were classified as sensitive or resistant to treatment based on the mean change in HbA1c levels. Using an assumption-free genome-wide association study, 45 single nucleotide polymorphisms (SNPs) involved in the therapeutic response to DPP-4 inhibitors (P < 1 × 10-4) were identified at or near PRKD1, CNTN3, ASK, and LOC10537792. A SNP located within the fourth intron of PRKD1 (rs57803087) was strongly associated with DPP-4 inhibitor response (P = 3.2 × 10-6). This is the first pharmacogenomics study on DPP-4 inhibitor treatment for diabetes in a Taiwanese population. Our data suggest that genes associated with β-cell function and apoptosis are involved in the therapeutic effect of DPP-4 inhibitors, even in the presence of additional oral anti-diabetic drugs. Our findings provide information on how genetic variants influence drug response and may benefit the development of personalized medicine.
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