KCNJ11 Lys23Glu and TCF7L2 rs290487(C/T) polymorphisms affect therapeutic efficacy of repaglinide in Chinese patients with type 2 diabetes.
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.
Yu
M
M
Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Hunan, People's Republic of China.
Xu
X-J
XJ
Yin
J-Y
JY
Wu
J
J
Chen
X
X
Gong
Z-C
ZC
Ren
H-Y
HY
Huang
Q
Q
Sheng
F-F
FF
Zhou
H-H
HH
Liu
Z-Q
ZQ
D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D001786:Blood Glucose / Q000187:drug effects / Q000235:genetics; D002219:Carbamates / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D018698:Glutamic Acid / Q000235:genetics*; D006801:Humans; D008239:Lysine / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000627:therapeutic use*; D011110:Polymorphism, Genetic / Q000235:genetics*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D012307:Risk Factors; D051820:TCF Transcription Factors / Q000235:genetics*; D058118:Transcription Factor 7-Like 2 Protein; D016896:Treatment Outcome; D000099161:Kcnj11 Channel
D001786:Blood Glucose; D002219:Carbamates; D018698:Glutamic Acid; D008239:Lysine; D010880:Piperidines; D024661:Potassium Channels, Inwardly Rectifying; D051820:TCF Transcription Factors; D058118:Transcription Factor 7-Like 2 Protein; D000099161:Kcnj11 Channel; C544894:TCF7L2 protein, human; C072379:repaglinide