Polymorphisms of the KCNQ1 gene are associated with the therapeutic responses of sulfonylureas in Chinese patients with type 2 diabetes.
KCNQ1 channel is a member of the voltage-gated potassium channel KQT-like subfamily. The KCNQ1 gene has recently been identified as a susceptibility locus for type 2 diabetes mellitus (T2DM). In the present study, we examined the effects of KCNQ1 variants on the therapeutic response to modified-release gliclazide (gliclazide MR) treatment in Chinese patients newly diagnosed with T2DM. A total of 100 newly diagnosed T2DM patients without a history of any anti-diabetic medications were treated with gliclazide MR for 16 weeks, but 91 patients completed the entire study. The anthropometric parameters were determined at baseline and at the final visit, while clinical laboratory tests were performed at baseline and on weeks 2, 4, 6, 12, 16. Two SNPs, rs2237892 and rs2237895, in the region of the KCNQ1 gene were genotyped in all the participants. All calculations and statistical analyses were conducted using SPSS. The rs2237892 TT homozygotes exhibited significantly higher 2-h glucose levels at baseline (P<0.05) and a lower cumulative attainment rate of the target 2-h glucose level (Plog-rank=0.020) than the C allele carriers. Patients with greater numbers of rs2237892 T alleles exhibited larger augmentations (Δ) in the 2-h glucose levels (P=0.027); and patients with the rs2237892 TT genotype exhibited a higher Δ homeostasis model assessment of β-cell function (HOMA-β) than CC and CT genotype carriers (P=0.021 and P=0.043, respectively). Moreover, the rs2237895 C allele was associated with a greater decrement in Δ glycated hemoglobin (HbA1c) (P=0.024); and patients with the CC genotype exhibited greater variance than those with the AA and AC genotypes (P=0.005 and 0.021, respectively). Compared with the C allele, the odds ratio for treatment success among carriers of the rs2237892 T allele was 2.533 (P=0.007); and the rs2237895 C allele was associated with a 2.360-fold decrease in HbA1c compared with the A allele (P=0.009). KCNQ1 polymorphisms are associated with gliclazide MR efficacy in Chinese patients with type 2 diabetes.
Department of Endocrinology & Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center of Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory for Diabetes Mellitus, Shanghai 200233, China.
Qing
Q
Li
Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China.
Ting-Ting
TT
Tang
Department of Endocrinology & Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center of Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory for Diabetes Mellitus, Shanghai 200233, China.
Feng
F
Jiang
Department of Endocrinology & Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center of Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory for Diabetes Mellitus, Shanghai 200233, China.
Rong
R
Zhang
Department of Endocrinology & Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center of Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory for Diabetes Mellitus, Shanghai 200233, China.
Miao
M
Chen
Department of Endocrinology & Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center of Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory for Diabetes Mellitus, Shanghai 200233, China.
Jun
J
Yin
Department of Endocrinology & Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center of Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory for Diabetes Mellitus, Shanghai 200233, China.
Yu-Qian
YQ
Bao
Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China.
Xiang
X
Cheng
Department of Endocrinology & Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center of Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory for Diabetes Mellitus, Shanghai 200233, China.|Shanghai Jiao Tong University Affiliated Sixth People's Hospital South Campus, Shanghai 201499, China.
Cheng
C
Hu
Department of Endocrinology & Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center of Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory for Diabetes Mellitus, Shanghai 200233, China.
Wei-Ping
WP
Jia
D000483:Alleles; D044466:Asian People / Q000235:genetics*; D001786:Blood Glucose / Q000187:drug effects; D002681:China / Q000208:ethnology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D005838:Genotype; D005907:Gliclazide / Q000494:pharmacology / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000187:drug effects; D006720:Homozygote; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013453:Sulfonylurea Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
D001786:Blood Glucose; D005907:Gliclazide; D006442:Glycated Hemoglobin; D051657:KCNQ1 Potassium Channel; D013453:Sulfonylurea Compounds; C496909:KCNQ1 protein, human; C517652:hemoglobin A1c protein, human
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