Pharmacogenetics of dipeptidyl peptidase 4 inhibitors in a Taiwanese population with type 2 diabetes.
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.
Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan.|Center for Personalized Medicine, China Medical University Hospital, Taichung, Taiwan.
Wen-Ling
WL
Liao
Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
Wen-Jane
WJ
Lee
Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, Taichung, Taiwan.|School of Chinese Medicine, China Medical University, Taichung, Taiwan.
Ching-Chu
CC
Chen
Department of Internal Medicine, Ditmanson Medical Foundation, Chiayi Christian Hospital, Chiayi City, Taiwan.|Department of Nursing, College of Nursing and Health Sciences, DAYEH University, Taiwan.|Department of Business management, College of Management, National Chung Cheng University, Taiwan.
Chieh Hsiang
CH
Lu
School of Chinese Medicine, China Medical University, Taichung, Taiwan.|National Center for Genome Medicine, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Chien-Hsiun
CH
Chen
National Center for Genome Medicine, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Yi-Chun
YC
Chou
Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans Hospital, Taichung, Taiwan.|School of Medicine, Chung Shan Medical University, Taichung, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.
I-Te
IT
Lee
Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans Hospital, Taichung, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.|School of Medicine, National Defense Medical Center, Taipei, Taiwan.|Institute of Medical Technology, National Chung-Hsing University, Taichung, Taiwan.
Wayne H-H
WH
Sheu
School of Chinese Medicine, China Medical University, Taichung, Taiwan.|National Center for Genome Medicine, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Jer-Yuarn
JY
Wu
National Center for Genome Medicine, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Chi-Fan
CF
Yang
Department of Genetics and Metabolism, Children's Hospital of China Medical University, Taichung, Taiwan.|School of Medicine, China Medical University, Taichung, Taiwan.
Chung-Hsing
CH
Wang
School of Chinese Medicine, China Medical University, Taichung, Taiwan.|Department of Medical Genetics, China Medical University Hospital, Taichung, Taiwan.|Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.
Fuu-Jen
FJ
Tsai
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D000071185:Pharmacogenomic Testing; D020641:Polymorphism, Single Nucleotide; D011493:Protein Kinase C / Q000235:genetics*; D012189:Retrospective Studies; D013624:Taiwan
D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; C089212:protein kinase D; D011493:Protein Kinase C
DPP-4 inhibitors; Taiwanese; pharmacogenetics; type 2 diabetes