Response to Sulphonylurea Treatment Is Related to Common Variants in [italic]TCF7L2 [/italic]and [italic]KCNQ1 [/italic]Genes

Response to Sulphonylurea Treatment Is Related to Common Variants in [italic]TCF7L2 [/italic]and [italic]KCNQ1 [/italic]Genes Almost 40 genes associated wit Almost 40 genes associated with type 2 diabetes (T2D) were detected by genome-wide association studies. The majority of them was shown to be associated with impaired insulin processing or secretion. The aim of the present pilot study was to analyse quantitative effects of treatment with sulphonylurea in addition to metformin on parameters of glycemic control in relation to common variants of genes associated with T2D and impaired insulin secretion. Eighty seven patients who failed to achieve optimal glycemic control on metformin monotherapy (HbA1c[lt]7%) were included in the present study. The effect of 6-month sulphonylurea therapy on glycemic control was evaluated with respect to polymorphisms in [italic]TCF7L2[/italic] rs7903146, [italic]KCNQ1 [/italic]rs163184, [italic]KCNJ11 [/italic]rs5219, [italic]MTNR1B [/italic]rs10830963,[italic] GIPR [/italic]rs10423928 and [italic]JAZF1 [/italic]rs864745. Gene variants were determined by real-time melting analysis. Reductions in HbA1c ([Delta]HbA1c) and fasting plasma glucose ([Delta]FPG) were the primary endpoints for the treatment efficacy. To account for baseline differences between the genotype groups, mean [Delta]HbA1c and [Delta]FPG values were adjusted in general linear models for age, sex, BMI and baseline HbA1c or FPG values. After sulphonylurea treatment, [Delta]HbA1c and [Delta]FPG were significantly lower in the risk T-allele carriers (CT+TT genotype) of [italic]TCF7L2[/italic] polymorphism when compared with the CC genotype group ([Delta]HbA1c: 0.86[plusmn]0.07 vs. 1.16[plusmn]0.07%, p=0.003; [Delta]FPG: 1.14[plusmn]0.14 vs. 1.57[plusmn]0.12 mmol/l, p=0.031, respectively). [Delta]FPG was significantly lower in the group of patients with the risk GG genotype of [italic]KCNQ1 [/italic]polymorphism when compared with the TT+TG genotype group (1.04[plusmn]0.18 vs. 1.58[plusmn]0.13 mmol/l, p=0.016). No significant relationships of [italic]KCNJ11, MTNR1B, GIPR [/italic]and [italic]JAZF1 [/italic]polymorphisms to glycemic response to sulphonylureas were observed. In conclusion, the degree of improvement of glycemic control after 6-month sulphonylurea treatment in addition to metformin in patients with type 2 diabetes is related to common variants in [italic]TCF7L2 [/italic]and [italic]KCNQ1[/italic]. The carriers of the risk genotypes had smaller improvements in the indices of glycemic control. IVAN TKAC, ZBYNEK SCHRONER, MARTIN JAVORSKY, LUCIA KLIMCAKOVA, VIERA HABALOVA, MARTINA DOBRIKOVA, JOZEF ZIDZIK, RUZENA TKACOVA 1408-P Kosice, Slovakia Genetics - Type 2 Diabetes