Variation in KCNQ1 is associated with therapeutic response to sulphonylureas

Abstract

SummaryBackgroundWe aimed to analyse quantitative effects of treatment with sulphonylurea in addition to metformin on parameters of glycemic control in relation to KCNQ1 genotypes, and to identify factors predictive for the response to sulphonylurea treatment.Material/MethodsEffect of 6-month sulphonylurea therapy in addition to metformin on glycemic control according to KCNQ1 genotypes was evaluated in 87 patients with type 2 diabetes who failed to achieve glycemic control on metformin monotherapy. KCNQ1 rs163184 (T>G) polymorphism was determined by real-time PCR with melting analysis of unlabeled probe.ResultsThe reduction in fasting plasma glucose (ΔFPG) after 6-month sulphonylurea therapy significantly differed among 3 KCNQ1 genotype groups (ANOVA, p=0.017). In a recessive genetic model, carriers of the T-allele (TT+TG) achieved significantly lower FPG levels in comparison with patients with the GG genotype (6.95±0.13 vs. 7.50±0.21 mmol/L, p=0.033). Consequently, ΔFPG was significantly higher in the TT+TG group compared to the GG group (1.58±0.13 vs. 1.04±0.18 mmol/L, p=0.016). In multiple linear regression analysis KCNQ1 genotype (p=0.016) and baseline FPG (p<0.001) were the only significant independent predictors of ΔFPG (R2=0.48).ConclusionsOur results suggest that the magnitude of FPG reduction after 6-month sulphonylurea treatment in addition to metformin in patients with type 2 diabetes is related to the variation in KCNQ1. The FPG response to sulphonylureas was significantly lower in carriers of the risk GG genotype.

Modify or die? - RNA modification defects in metazoans

“…38 Human carriers of TIID alleles show reduced levels of ms 2 t 6 A 37 , they fail to generate and to secrete insulin, and they may respond differently to pharmacological treatment of TIID. [40][41][42][43][44] Consistent with this, CDKAL1 alleles correlate strongly with an increased risk for coronary artery diseases, most likely as a downstream effect of TIID. 45 Furthermore, CDKAL1 was identified as a risk factor for Crohn's disease (CD) and for Psoriasis.…”

Association of KCNQ1 polymorphisms with gliclazide efficacy in Chinese type 2 diabetic patients

“…To the best of our knowledge, only two studies have reported the association of KCNQ1 polymorphisms with response to SUs and their results were inconclusive. In a White population, a study including 87 patients with T2DM treated with SUs in addition to metformin for 6 months found a significant genotype-specific effect of rs163184 on the reduction in FPG, with a significantly lower reduction in patients with the GG genotype (P =0.016) [27]. Because the association between rs163184 and T2DM has rarely been reported in the Chinese Han population [34], we did not include rs163184 in our study for the moment.…”

“…have evaluated the association of KCNQ1 polymorphisms with SUs response and their results are conflicting [16,27].…”

Polymorphisms of the KCNQ1 gene are associated with the therapeutic responses of sulfonylureas in Chinese patients with type 2 diabetes

“…Thus far, to the best of our knowledge, two studies have assessed the KCNQ1 gene and the therapeutic response to SU treatment. The first study evaluated KCNQ1 (rs163184) and the therapeutic response (FPG, HbA1c) to sulfonylurea treatment [38] . However, the patients who were not newly diagnosed with T2DM in this study were not treated with SU monotherapy, and other parameters related to insulin sensitivity and β-cell function were not assessed.…”