PMID- 27694910 OWN - NLM STAT- MEDLINE DCOM- 20170803 LR - 20221207 IS - 1745-7254 (Electronic) IS - 1671-4083 (Print) IS - 1671-4083 (Linking) VI - 38 IP - 1 DP - 2017 Jan TI - Polymorphisms of the KCNQ1 gene are associated with the therapeutic responses of sulfonylureas in Chinese patients with type 2 diabetes. PG - 80-89 LID - 10.1038/aps.2016.103 [doi] AB - 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 (P(log-rank)=0.020) than the C allele carriers. Patients with greater numbers of rs2237892 T alleles exhibited larger augmentations (Delta) in the 2-h glucose levels (P=0.027); and patients with the rs2237892 TT genotype exhibited a higher Delta homeostasis model assessment of beta-cell function (HOMA-beta) 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 Delta 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. FAU - Li, Qing AU - Li Q AD - 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. FAU - Tang, Ting-Ting AU - Tang TT AD - Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China. FAU - Jiang, Feng AU - Jiang F AD - 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. FAU - Zhang, Rong AU - Zhang R AD - 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. FAU - Chen, Miao AU - Chen M AD - 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. FAU - Yin, Jun AU - Yin J AD - 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. FAU - Bao, Yu-Qian AU - Bao YQ AD - 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. FAU - Cheng, Xiang AU - Cheng X AD - Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China. FAU - Hu, Cheng AU - Hu C AD - 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. AD - Shanghai Jiao Tong University Affiliated Sixth People's Hospital South Campus, Shanghai 201499, China. FAU - Jia, Wei-Ping AU - Jia WP AD - 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. LA - eng PT - Clinical Trial PT - Journal Article DEP - 20161003 PL - United States TA - Acta Pharmacol Sin JT - Acta pharmacologica Sinica JID - 100956087 RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin A) RN - 0 (KCNQ1 Potassium Channel) RN - 0 (KCNQ1 protein, human) RN - 0 (Sulfonylurea Compounds) RN - 0 (hemoglobin A1c protein, human) RN - G4PX8C4HKV (Gliclazide) SB - IM MH - Alleles MH - Asian People/*genetics MH - Blood Glucose/drug effects MH - China/ethnology MH - Diabetes Mellitus, Type 2/*drug therapy/*genetics MH - Female MH - Genotype MH - Gliclazide/pharmacology/*therapeutic use MH - Glycated Hemoglobin/drug effects MH - Homozygote MH - Humans MH - KCNQ1 Potassium Channel/*genetics MH - Male MH - Middle Aged MH - Polymorphism, Single Nucleotide/*genetics MH - Sulfonylurea Compounds/pharmacology/*therapeutic use MH - Treatment Outcome PMC - PMC5220536 EDAT- 2016/10/04 06:00 MHDA- 2017/08/05 06:00 PMCR- 2018/01/01 CRDT- 2016/10/04 06:00 PHST- 2016/06/01 00:00 [received] PHST- 2016/08/25 00:00 [accepted] PHST- 2016/10/04 06:00 [pubmed] PHST- 2017/08/05 06:00 [medline] PHST- 2016/10/04 06:00 [entrez] PHST- 2018/01/01 00:00 [pmc-release] AID - aps2016103 [pii] AID - 10.1038/aps.2016.103 [doi] PST - ppublish SO - Acta Pharmacol Sin. 2017 Jan;38(1):80-89. doi: 10.1038/aps.2016.103. Epub 2016 Oct 3.