title: Effects of KCNQ1 polymorphisms on the therapeutic efficacy of oral antidiabetic drugs in Chinese patients with type 2 diabetes.
abstract: 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 (HOMA-IR) (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 rosiglitazone cohort (P = 0.0321). Our results indicated that KCNQ1 polymorphisms are associated with repaglinide efficacy, and might also be associated with rosiglitazone response, in Chinese patients with type 2 diabetes.
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China.
authors.forename: W
authors.initials: W
authors.lastname: Yu
authors.forename: C
authors.initials: C
authors.lastname: Hu
authors.forename: R
authors.initials: R
authors.lastname: Zhang
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.forename: W
authors.initials: W
authors.lastname: Qin
authors.forename: J
authors.initials: J
authors.lastname: Lu
authors.forename: F
authors.initials: F
authors.lastname: Jiang
authors.forename: S
authors.initials: S
authors.lastname: Tang
authors.forename: Y
authors.initials: Y
authors.lastname: Bao
authors.forename: K
authors.initials: K
authors.lastname: Xiang
authors.forename: W
authors.initials: W
authors.lastname: Jia
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000483:Alleles; D044466:Asian People; D001786:Blood Glucose / Q000187:drug effects; D002219:Carbamates / Q000494:pharmacology / Q000627:therapeutic use*; D002681:China; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D051657:KCNQ1 Potassium Channel / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D002219:Carbamates; D007004:Hypoglycemic Agents; D007328:Insulin; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D010880:Piperidines; D045162:Thiazolidinediones; D000077154:Rosiglitazone; C072379:repaglinide