Discovery of DiPeptidyl Peptidase-4 Gene Variants and the Associations with Efficacy of Vildagliptin in Patients with Type 2 Diabetes - A Pilot Study

Abstract

Background: The dipeptidyl peptidase-4 (DPP4) inhibitors have become widely used antidiabetic medication. They control glycemia by interacting with serum DPP4 to interfere catalyzation of incretins. The aim of this pilot study was to discover the DPP4 polymorphisms that could affect the efficacy of vildagliptin, a DPP-4 inhibitor in diabetic patients. Methods: Genetic variations in DPP4 were identified in 48 patients with type 2 diabetes who received vildagliptin treatment at least 12 weeks following metformin monotherapy. Luciferase assay was performed to estimate the effect of the regulatory single nucleotide polymorphism (SNP) on expression of DPP4. Results: Eight tagging SNPs were genotyped in a sample of 24 patients. Additional sample of 24 patients was used to discover further regulatory SNPs and coding SNPs. In all 48 patients, responders (degree of HbA1c and/or fasting glucose level decrease greater than 10% of baseline after 12 weeks of vildagliptin add-on treatment) did not show any significant difference in selected six DPP4 polymorphisms from non-responders. DPP4 expression was not different according to g.-234A/C in luciferase assay. Conclusion: Our pilot study could not find any significant genetic variant which is associated with vildagliptin response in patients with type 2 diabetes. Further studies in large population are warranted.