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A genetic variant in GLP1R is associated with response to DPP-4 inhibitors in patients with type 2 diabetes

 Eugene Han  ;  Hye Sun Park  ;  Obin Kwon  ;  Eun Yeong Choe  ;  Hye Jin Wang  ;  Yong-ho Lee  ;  Sang-Hak Lee  ;  Chul Hoon Kim  ;  Lee-Kyung Kim  ;  Soo Heon Kwak  ;  Kyong Soo Park  ;  Chul Sik Kim  ;  Eun Seok Kang 
 MEDICINE, Vol.95(44) : 5155, 2016 
Journal Title
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Incretin hormone-based therapy in type 2 diabetes has been widely used, and dipepdityl peptidase-4 (DPP-4) inhibitors, which prevent incretin degradation, have become popular oral hypoglycemic agents. The efficacy of DPP-4 inhibitors varies from individuals, and factors determining responses to DPP-4 inhibitors have not been fully established. We aimed to investigate whether genetic variations in glucagon-like peptide (GLP-1) receptor are associated with responses to DPP-4 inhibitors in patients with type 2 diabetes.Genetic variations of rs3765467 in GLP-1 receptor were explored in 246 patients with type 2 diabetes who received DPP-4 inhibitors treatment for 24 weeks in addition to previous medication. Patients with glycated hemoglobin (HbA1c) > 7% and who were naive to any DPP-4 inhibitors were enrolled. Responders were defined as those who showed a > 10% reduction in HbA1c after DPP-4 inhibitor treatment.DPP-4 inhibitors improved glycemic parameters and lipid profiles. Compared to the major genotype (GG), a larger proportion of patients with the minor allele genotype (GA/AA) were responders (P?=?0.018), and also showing greater HbA1c reductions (1.3?±?1.1 vs 0.9?±?1.2%; P?=?0.022). This genetic effect remained significant even after adjustment for other confounding factors (OR?=?2.00, 95% CI?=?1.03-3.89).Polymorphism in the GLP-1 receptor may influence DPP-4 inhibitor response. Further studies in larger population will help determine the association between genetic variation and interindividual differences in DPP-4 inhibitor therapy.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kang, Eun Seok(강은석) ORCID logo https://orcid.org/0000-0002-0364-4675
Kim, Chul Hoon(김철훈) ORCID logo https://orcid.org/0000-0002-7360-429X
Park, Hye Sun(박혜선)
Wang, Hye Jin(왕혜진)
Lee, Sang Hak(이상학) ORCID logo https://orcid.org/0000-0002-4535-3745
Lee, Yong Ho(이용호) ORCID logo https://orcid.org/0000-0002-6219-4942
Han, Eu Gene(한유진)
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