Association between the clinical effect of DPP-4 inhibitors and the genetic polymorphism of BDNF gene

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07855
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Iwate Medical University
• Principal Investigator: Yoshihiko Takahashi 岩手医科大学, 医学部, 准教授 (80415562)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 脳由来神経栄養因子 / DPP-4阻害薬 / 遺伝子多型 / 2型糖尿病

Outline of Final Research Achievements

We studied whether or not the effectiveness of DPP-4 inhibitors is associated with a single nucleotide polymorphism of the BDNF gene, rs6265(G→A), and physical activity (PA). Non-responders were defined as patients who showed less than 0.2% improvement of HbA1c 3 or 4 months after starting the medication, and PA was evaluated using a questionnaire. Among 99 patients after exclusion of metformin users, the non-responder rates of G/* with lower PA, G/* with higher PA, A/A with lower PA, and A/A with higher PA, were 56.8%, 28.6%, 25.0%, and 20.0%, respectively (p=0.037). This finding was similarly observed in a multivariate model. We propose a hypothesis that, in G/* patients who preserve activity-dependent secretion of BDNF, PA might be more important for the effectiveness of DPP-4 inhibitors than in A/A patients who are defective for that type of secretion.

Free Research Field

糖尿病学

Academic Significance and Societal Importance of the Research Achievements

BDNFは身体活動量の増加により分泌が増加し、インスリン抵抗性改善やインスリン分泌改善など糖代謝に有効である。その一塩基多型 rs6265は日本人でも頻度の高い遺伝子多型である。一方DPP-4阻害薬は日本人2型糖尿病において最も多く投与され、低血糖などの副作用が低く高齢者などでも安全に使用できる。しかし一部の患者においては無効であることが知られており、どのような患者に投与するべきか、あるいはどのように生活習慣を修飾すれば有効性が高まるかということは、糖尿病治療の上で重要である。遺伝子多型と運動とが薬剤の有効性に関連する可能性を示した点は、個人の特質を考慮した医療という観点で有意義である。