KCNQ1 gene polymorphism is associated with glycaemic response to treatment with DPP-4 inhibitors

Abstract Aims Only a few gene variants were associated with the response to dipeptidylpeptidase-4 inhibitors (DPP4I). KCNQ1 gene variants were previously related both to type 2 diabetes (T2D) and incretin effect. We hypothesized that T2D related KCNQ1 variants would be associated with smaller glucose-lowering effect of DDP4I. Methods We performed a retrospective study in 137 Caucasian subjects with T2D who were followed for 6 months after initiation of DPP4I treatment. Genotyping for KCNQ1 rs163184 and rs151290 was performed using PCR-HRMA and PCR-RFLP methods, respectively. The main clinical outcome was reduction in HbA1c (ΔHbA1c) after 6-month DPP4I treatment. Results KCNQ1 rs163184 T > G variant was associated with the response to DPP4I treatment in genetic additive model ( β  = −0.30, p  = 0.022). For each G allele in the rs163184 genotype, we observed a 0.3% (3.3 mmol/mol) less reduction in HbA1c during treatment with a DPP4I. Both the GG homozygotes and G-allele carriers had significantly smaller HbA1c reduction in comparison with the TT homozygotes. Conclusions KCNQ1 rs163184 T > G variant was associated with a reduced glycaemic response to DPP4I. The difference of 0.6% (6.5 mmol/mol) in HbA1c reduction between the TT and GG homozygotes might be of clinical significance if replicated in further studies.