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KCNJ11 Lys23Glu and TCF7L2 rs290487(C/T) Polymorphisms Affect Therapeutic Efficacy of Repaglinide in Chinese Patients With Type 2 Diabetes
Author(s) -
Yu M,
Xu XJ,
Yin JY,
Wu J,
Chen X,
Gong ZC,
Ren HY,
Huang Q,
Sheng FF,
Zhou HH,
Liu ZQ
Publication year - 2010
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2009.242
Subject(s) - repaglinide , medicine , tcf7l2 , type 2 diabetes mellitus , genotype , postprandial , type 2 diabetes , endocrinology , body mass index , gastroenterology , diabetes mellitus , glycated hemoglobin , insulin , biology , single nucleotide polymorphism , genetics , gene
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. Clinical Pharmacology & Therapeutics (2010) 87 3, 330–335. doi: 10.1038/clpt.2009.242