4.6 Article

KCNJ11 Lys23Glu and TCF7L2 rs290487(C/T) Polymorphisms Affect Therapeutic Efficacy of Repaglinide in Chinese Patients With Type 2 Diabetes

Journal

CLINICAL PHARMACOLOGY & THERAPEUTICS
Volume 87, Issue 3, Pages 330-335

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/clpt.2009.242

Keywords

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Funding

  1. National Major Project of Science and Technology of China [2009ZX09304]
  2. National Natural Science Foundation of China [30572230, 30873089]
  3. Natural Science Foundation of Hunan Province of China [08JJ3058]
  4. Changsha Municipal Science and Technology Plan of China [K0802148-31]

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This study showed that the polymorphisms KCNJ11 Lys23Glu and TCF7L2 rs290487(C/T) are associated with a heightened risk of developing type 2 diabetes mellitus (T2DM). We also explored the effects of these polymorphisms on the efficacy of repaglinide therapy in Chinese patients with T2DM. A total of 259 patients with T2DM and 188 healthy controls were genotyped. Forty patients with various genotypes were randomly selected to undergo an 8-week repaglinide treatment regimen. Patients with the G allele of the KCNJ11 Lys23Glu polymorphism showed higher levels of fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) (P < 0.05). After repaglinide treatment, patients with the GA or AA genotype showed higher levels of FPG, PPG, and glycated hemoglobin (HbA(1c)) compared with patients with the GG genotype (P < 0.05). Patients with the C allele of TCF7L2 rs290487(C/T) had higher total cholesterol levels and lower body mass index (BMI) (P < 0.05). In patients with the TT genotype, the drug showed better efficacy with respect to levels of fasting insulin, triglycerides, and low-density lipoprotein cholesterol (LDL-c) than in patients with the CC or CT genotype (P < 0.05). The KCNJ11 and TCF7L2 polymorphisms were associated with repaglinide efficacy.

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