Gotthardová Ivana, Javorský Martin, Klimčáková Lucia, Kvapil Milan, Schroner Zbynek, Kozárová Miriam, Malachovská Zuzana, Ürgeová Anna, Židzik Jozef, Tkáč Ivan
P.J. Šafárik University, Faculty of Medicine, Košice, Slovakia; L. Pasteur University Hospital, Košice, Slovakia.
P.J. Šafárik University, Faculty of Medicine, Košice, Slovakia.
Diabetes Res Clin Pract. 2017 Aug;130:142-147. doi: 10.1016/j.diabres.2017.05.018. Epub 2017 May 19.
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.
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.
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.
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.
仅有少数基因变异与二肽基肽酶-4抑制剂（DPP4I）的反应相关。KCNQ1基因变异先前与2型糖尿病（T2D）及肠促胰岛素效应均有关。我们推测，与T2D相关的KCNQ1变异会与DPP4I较小的降糖作用相关。
我们对137例患有T2D的白种人受试者进行了一项回顾性研究，这些受试者在开始DPP4I治疗后随访6个月。分别采用PCR-HRMA和PCR-RFLP方法对KCNQ1 rs163184和rs151290进行基因分型。主要临床结局是DPP4I治疗6个月后糖化血红蛋白（HbA1c）的降低（ΔHbA1c）。
在遗传加性模型中，KCNQ1 rs163184 T>G变异与DPP4I治疗反应相关（β=-0.30，p=0.022）。对于rs163184基因型中的每个G等位基因，我们观察到在使用DPP4I治疗期间HbA1c降低少0.3%（3.3 mmol/mol）。与TT纯合子相比，GG纯合子和G等位基因携带者的HbA1c降低均显著较小。
KCNQ1 rs163184 T>G变异与对DPP4I的血糖反应降低相关。如果在进一步研究中得到重复，TT和GG纯合子之间HbA1c降低0.6%（6.5 mmol/mol）的差异可能具有临床意义。
