KCNQ1 gene polymorphism is associated with glycaemic response to treatment with DPP-4 inhibitors
Language English Country Ireland Media print-electronic
Document type Journal Article
PubMed
28624668
DOI
10.1016/j.diabres.2017.05.018
PII: S0168-8227(17)30329-7
Knihovny.cz E-resources
- Keywords
- DPP-4 inhibitors, KCNQ1, Pharmacogenetics, Type 2 diabetes,
- MeSH
- Alleles MeSH
- Diabetes Mellitus, Type 2 drug therapy genetics MeSH
- KCNQ1 Potassium Channel genetics MeSH
- Genotype MeSH
- Glycated Hemoglobin analysis MeSH
- Dipeptidyl-Peptidase IV Inhibitors therapeutic use MeSH
- Blood Glucose analysis MeSH
- Middle Aged MeSH
- Humans MeSH
- Polymorphism, Genetic genetics MeSH
- Retrospective Studies MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- KCNQ1 Potassium Channel MeSH
- Glycated Hemoglobin A MeSH
- Dipeptidyl-Peptidase IV Inhibitors MeSH
- Blood Glucose MeSH
AIMS: Only afew 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 6months 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% (3.3mmol/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% (6.5mmol/mol) in HbA1c reduction between the TT and GG homozygotes might be of clinical significance if replicated in further studies.
L Pasteur University Hospital Košice Slovakia
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