Type 2 diabetes, characterized by chronic hyperglycemia caused by insulin resistance and β-cell dysfunction, has become a worldwide public health problem, 1 leading to considerable emphasis on the management of type 2 diabetes. Oral antidiabetic drugs are among the most widely prescribed of all medications for lowering of glucose levels. These include metformin, sulfonylureas, glinides, α-glucosidase inhibitors, and thiazolidinediones. 2 However, there is interindividual variability in the responses to these drugs, partly attributable to genetic factors implicated in drug absorption, distribution, metabolism, and target. 3 Variants in CYP2C8, SLCO1B1, KCNJ11, ABCC8, NOS1AP, and TCF7L2 were previously found to be associated with repaglinide efficacy, 4-8 whereas variants in CYP2C8, PPARG, UCP2, ADRB3, TNF-α, and ABCA1 were shown to be associated with rosiglitazone treatment outcome. [9][10][11][12][13] Recently, after genome-wide association studies in East Asians, 14,15 replicated in the population of mainland China, 16 KCNQ1 has been identified as a susceptibility gene for type 2 diabetes. However, whether KCNQ1 single-nucleotide polymorphisms (SNPs) have an impact on the therapeutic effects of oral antihyperglycemic drugs remains unknown. Consequently, we conducted this study aimed at evaluating the effects of these polymorphisms on the efficacy of repaglinide and rosiglitazone in newly diagnosed patients with type 2 diabetes. ResultsA total of 91 patients treated with repaglinide completed the 48-week follow-up. Of the 13 subjects who were withdrawn from the study, 4 had glycated hemoglobin (HbA 1c ) ≥8% at two consecutive time points, and 9 were lost to follow-up. Simultaneously, in the rosiglitazone cohort, 1 patient with elevated hepatic enzymes and 5 patients with inadequate control of blood glucose or HbA 1c were excluded, and 6 patients were lost to follow-up, leaving a sample of 93 patients who completed the whole study (see Supplementary Table S1 online).All the SNPs conformed to Hardy-Weinberg equilibrium in each cohort.The aim of this study was to explore the impact of KCNQ1 variants on the responses to oral antidiabetic drugs in a Chinese study population. a 48-week randomized pharmacogenetics study compared the effects of repaglinide and rosiglitazone in 209 newly diagnosed patients with type 2 diabetes. in the repaglinide cohort, individuals who were rs2237892 TT homozygotes exhibited lower 2-h glucose levels and significantly higher cumulative attainment rates of target 2-h glucose levels (P log-rank = 0.0383) than the C allele carriers; patients with a greater number of rs2237892 C alleles showed larger augmentations in both fasting insulin and homeostasis model assessment of insulin resistance (homair) (P = 0.0166 and 0.0026, respectively); moreover, the rs2237895 C allele was also associated with greater increments in both fasting insulin and homa-ir (P = 0.0274 and 0.0259, respectively). in contrast, only an association between rs2237897 and decrease in 2-h glucose levels was detected in the...
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